Identification

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Name
Conjugated estrogens
Accession Number
DB00286  (APRD00396)
Type
Small Molecule
Groups
Approved
Description

The conjugated estrogens are noncrystalline mixtures of purified female sex hormones obtained either by its isolation from the urine of pregnant mares or by synthetic generation from vegetal material. Both of these products are later conjugated to natrium sulfate by ester bonds in order to make them more water soluble.[10, 7]

The conjugated estrogen product contains a mix of estrogen from which about 50% is represented by estrone sulfate followed by 25% of equilin sulfate, 15% of 17-alpha-dehydroequilenin sulfate, 3% of equilenin sulfate, 5% of 17-alpha and 17-beta-dihydroequilenin sulfate, 2% of 17-alpha-estradiolsulfate and 3% of 17-beta-estradiolsulfate. It also presents a large number of unidentified molecules with weak estrogenic activity as well as non-human molecules when it is obtained from pregnant mares urine.[7]

The conjugated estrogen mixture was approved for marketing in US in 1942 based on the efficacy against certain conditions. However, until 1986 official clinical trials were performed and this product was determined to be effective for the treatment of osteoporosis.[9] The currently approved product of conjugated estrogens was developed by Wyeth Ayerst and FDA approved in 2003.[11]

Synonyms
  • Conjugated equine estrogens
  • conjugated estrogens
  • Estrogens, Conjugated
  • Estrogens,conjugated
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
C.E.S. TabletsTablet1.25 mgOralValeant Canada Lp Valeant Canada S.E.C.1963-12-312014-07-30Canada
C.E.S. TabletsTablet0.3 mgOralValeant Canada Lp Valeant Canada S.E.C.1997-03-142014-07-30Canada
C.E.S. TabletsTablet0.9 mgOralValeant Canada Lp Valeant Canada S.E.C.1997-03-142014-07-30Canada
C.E.S. TabletsTablet0.625 mgOralValeant Canada Lp Valeant Canada S.E.C.1963-12-31Not applicableCanada
Congest Tab 0.3mgTablet0.3 mgOralLaboratoires Trianon Inc1990-12-31Not applicableCanada
Congest Tab 0.625mgTablet0.625 mgOralLaboratoires Trianon Inc1990-12-31Not applicableCanada
Congest Tab 0.9mgTablet0.9 mgOralLaboratoires Trianon Inc1990-12-31Not applicableCanada
Congest Tab 1.25mgTablet1.25 mgOralLaboratoires Trianon Inc1990-12-31Not applicableCanada
Congest Tab 2.5mgTablet2.5 mgOralLaboratoires Trianon Inc1990-12-31Not applicableCanada
PremarinInjection, powder, lyophilized, for solution25 mg/5mLIntramuscular; IntravenousWyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc.1956-12-01Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-conest Tab 0.3mgTablet0.3 mgOralApotex Corporation1994-12-312009-10-09Canada
Apo-conest Tab 0.625mgTablet0.625 mgOralApotex Corporation1994-12-312009-10-09Canada
Apo-conest Tab 0.9mgTablet0.9 mgOralApotex Corporation1994-12-312009-10-09Canada
Apo-conest Tab 1.25mgTablet1.25 mgOralApotex Corporation1994-12-312009-10-09Canada
Apo-conest Tab 2.5mgTablet2.5 mgOralApotex Corporation1994-12-312009-10-09Canada
PMS-conjugated Estrogens C.S.D.Tablet0.625 mgOralPharmascience Inc1983-12-31Not applicableCanada
PMS-conjugated Estrogens C.S.D.Tablet1.25 mgOralPharmascience Inc1983-12-31Not applicableCanada
PMS-conjugated Estrogens C.S.D.Tablet0.3 mgOralPharmascience Inc1999-03-03Not applicableCanada
PMS-conjugated Estrogens C.S.D.Tablet0.9 mgOralPharmascience Inc1999-03-03Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DuaveeConjugated estrogens (0.45 mg/1) + Bazedoxifene acetate (20 mg/1)Tablet, film coatedOralWyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc.2013-10-03Not applicableUs
DuaveeConjugated estrogens (0.45 mg/1) + Bazedoxifene acetate (20 mg/1)Tablet, film coatedOralU.S. Pharmaceuticals2013-11-15Not applicableUs
DuaveeConjugated estrogens (0.45 mg/1) + Bazedoxifene acetate (20 mg/1)Tablet, film coatedOralU.S. Pharmaceuticals2013-11-15Not applicableUs
DuaviveConjugated estrogens (0.45 mg) + Bazedoxifene (20 mg)Tablet, multilayer, extended releaseOralPfizer Europe Ma Eeig2014-12-16Not applicableEu
DuaviveConjugated estrogens (0.45 mg) + Bazedoxifene (20 mg)Tablet, multilayer, extended releaseOralPfizer2016-12-20Not applicableCanada
PremphaseConjugated estrogens (0.625 mg/1) + Conjugated estrogens (0.625 mg/1) + Medroxyprogesterone acetate (5 mg/1)KitPhysicians Total Care, Inc.2005-07-08Not applicableUs
PremphaseConjugated estrogens (0.625 mg/1) + Conjugated estrogens (0.625 mg/1) + Medroxyprogesterone acetate (5 mg/1)KitWyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc.2012-03-01Not applicableUs
PremphaseConjugated estrogens (0.625 mg/1) + Conjugated estrogens (0.625 mg/1) + Medroxyprogesterone acetate (5 mg/1)KitWyeth Pharmaceuticals Inc.1995-12-012009-10-23Us
PremphaseConjugated estrogens (0.625 mg/1) + Conjugated estrogens (0.625 mg/1) + Medroxyprogesterone acetate (5 mg/1)KitWyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc.2012-03-01Not applicableUs
PremphaseConjugated estrogens (0.625 mg/1) + Conjugated estrogens (0.625 mg/1) + Medroxyprogesterone acetate (5 mg/1)KitWyeth Pharmaceuticals Inc.1995-12-012009-10-23Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Esterified Estrogens and MethyltestosteroneConjugated estrogens (0.625 mg/1) + Methyltestosterone (1.25 mg/1)TabletOralAmneal Pharmaceuticals of New York Llc2010-09-22Not applicableUs53746 0077 01 nlmimage10 6605b34d
Esterified Estrogens and MethyltestosteroneConjugated estrogens (1.25 mg/1) + Methyltestosterone (2.5 mg/1)TabletOralAmneal Pharmaceuticals of New York Llc2010-09-22Not applicableUs53746 0078 01 nlmimage10 5f05afed
Esterified Estrogens and MethyltestosteroneConjugated estrogens (0.625 mg/1) + Methyltestosterone (1.25 mg/1)Tablet, film coatedOralSeton Pharmaceuticals2005-10-102017-02-23Us
Esterified Estrogens and MethyltestosteroneConjugated estrogens (1.25 mg/1) + Methyltestosterone (2.5 mg/1)Tablet, film coatedOralSeton Pharmaceuticals2010-05-052017-01-26Us
Categories
UNII
IU5QR144QX
CAS number
12126-59-9
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

The conjugated estrogens are indicated for several different conditions including:

  • Treatment of moderate to severe vasomotor symptoms due to menopause.
  • Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause.
  • Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure.
  • Palliative treatment of breast cancer in appropriately selected patients with metastatic disease.
  • Palliative treatment of androgen-dependent carcinoma of the prostate.
  • Preventive therapy of postmenopausal osteoporosis.[2]
Associated Conditions
Pharmacodynamics

The binding of estrogens to the estrogen receptor produces the activation of nuclear receptors in order to bind to estrogen response elements in certain target genes. This mechanistic cascade results in histone acetylation, alteration of chromatin conformation and the initiation of transcription of certain specific drugs.[10]

In preclinical studies, the conjugated estrogens are known to have a similar estrogenic potency than estrone and the equilin components of the conjugated estrogens have similar potency in the liver when compared to bioidentical estradiol.[4] It has also been tested and confirmed that conjugated estrogens present a selective estrogen receptor modulator profile which allows it to have a large beneficial effect on the bone and cardiovascular system.[5]

Clinically, the administration of conjugated estrogens is known to promote vasomotor stability, maintain genitourinary function, and normal growth and development of female sex hormones. It has also been shown to prevent accelerated bone loss by inhibiting bone resorption and restoring the balance of bone resorption. In the hormonal area, it is shown to inhibit luteinizing hormone and decrease the serum concentration of testosterone.[8]

Mechanism of action

The conjugated estrogens, equally to the normal physiological estrogen, work by agonistically binding to the estrogen receptors alpha and beta. The estrogen receptors vary in quantity and proportion according to the tissues and hence, the activity of this conjugated estrogens is very variable.[2]

The activity made by the conjugated estrogens is driven by the increase in the synthesis of DNA, RNA and various proteins in responsive tissues which in order will reduce the release of gonadotropin-releasing hormone, follicle-stimulating hormone and leuteinizing hormone.[8]

The specific mechanism of action cannot be described only in terms of total estrogenic action as the pharmacokinetic profile, the tissue specificity and the tissue metabolism is different for each component of the product.[7]

TargetActionsOrganism
AEstrogen receptor alpha
agonist
Humans
AEstrogen receptor beta
agonist
Humans
Absorption

The conjugated estrogens are well absorbed in the gastrointestinal tract and the maximum plasma concentration of the conjugated estrogens is reached after 7 hours depending on the estrone component.[1] The maximal plasma concentration of conjugated estrogens after multiple doses of 0.45 mg is reported to be of 2.6 ng/ml with an AUC in the steady state of 35 ng.h/ml.[2] Unconjugated estrogens are known to be cleared from the circulation at a faster rate than their ester forms.[3]

Volume of distribution

The physiological distribution of estrogens in the body is very similar to what is seen in endogenous estrogens and hence, it is widely distributed.[2] The conjugated estrogens are mainly found in the sex hormone target organs.[12]

Protein binding

Conjugated estrogens are bound to plasma proteins and this bound state can represent around 50-80% of the administered dose.[8] It circulates in the blood mainly bound to sex-hormone binding globulin and albumin.[2]

Metabolism

The conjugated estrogens are metabolized by a number of different pathways. One of the metabolic pathways of the conjugated estrogens is driven by the action of the cytochrome isoenzyme CYP3A4.[1] On the other hand, the conjugated estrogens can also be processed by a dynamic equilibrium of metabolic interconversion and sulfate conjugation. Some of the principal metabolic reactions of the conjugated estrogens are driven by the conversion of 17beta-estradiol to estrone and the further change to estriol. A portion of the administered conjugated estrogens will remain in the blood as sulfate conjugates which serve as a circulating reservoir for the generation of new estrogens.[2]

In the endometrium, equilin is metabolized to 2-hydroxy and 4-hydroxy equilin as well as 2-hydroxy and 4-hydroxy estradiol. This hydroxylation process is very large in various of the components of the conjugated estrogens and hence, the major metabolites in urine are known to be 17-ketosteroid-16-alpha-hydroxy estrone, 16-alpha-hydroxy-17-beta-dihydro equilin and 16-alpha-hydroxy-17-beta-dihydroequilenin.[3]

Route of elimination

The conjugated estrogens are eliminated mainly in the urine.[1] In this renal elimination, it is possible to find 17 beta-estradiol, estrone, estriol, as well as the glucuronide and sulfate conjugates of the estrogens.[2]

Half life

The median half-life of the conjugated estrogens is reported to be of 17 hours.[1]

Clearance

The reported normal clearance rate for estrogens is of approximately 615 L/m2.[6]

Toxicity

The reported oral LD50 in the rat is of more than 5000 mg/kg.[13] Serious overdosage symptoms have not been reported. There have been only reports of nausea, vomiting, and withdrawal in bleeding in females.[Label]

Long-term continuous administration of estrogens is correlated to increased risk on the incidence of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.[Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinConjugated estrogens may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinConjugated estrogens may decrease the anticoagulant activities of (S)-Warfarin.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Conjugated estrogens.
3,5-DinitrocatecholThe metabolism of Conjugated estrogens can be decreased when combined with 3,5-Dinitrocatechol.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Conjugated estrogens.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Conjugated estrogens.
6-Deoxyerythronolide BThe metabolism of Conjugated estrogens can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Conjugated estrogens.
7-ethyl-10-hydroxycamptothecinThe metabolism of Conjugated estrogens can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Conjugated estrogens.
Food Interactions
Not Available

References

Synthesis Reference
US20020156303
General References
  1. Authors unspecified: Conjugated oestrogens/bazedoxifene. Aust Prescr. 2017 Jun;40(3):114-115. doi: 10.18773/austprescr.2017.039. Epub 2017 May 10. [PubMed:28798519]
  2. Cada DJ, Baker DE: Conjugated estrogens and bazedoxifene. Hosp Pharm. 2014 Mar;49(3):273-83. doi: 10.1310/hpj4903-273. [PubMed:24715748]
  3. Bhavnani BR: Pharmacokinetics and pharmacodynamics of conjugated equine estrogens: chemistry and metabolism. Proc Soc Exp Biol Med. 1998 Jan;217(1):6-16. [PubMed:9421201]
  4. Kuhl H: Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005 Aug;8 Suppl 1:3-63. doi: 10.1080/13697130500148875. [PubMed:16112947]
  5. Cline JM: Assessing the mammary gland of nonhuman primates: effects of endogenous hormones and exogenous hormonal agents and growth factors. Birth Defects Res B Dev Reprod Toxicol. 2007 Apr;80(2):126-46. doi: 10.1002/bdrb.20112. [PubMed:17443713]
  6. Hembree WC, Bardin CW, Lipsett MB: A study of estrogen metabolic clearance rates and transfer factors. J Clin Invest. 1969 Oct;48(10):1809-19. doi: 10.1172/JCI106147. [PubMed:5822587]
  7. Lauritzen C. and Studd J. (2005). Current management of the menopause. Taylor and Francis. [ISBN:0-203-62272-3]
  8. Arthur H. Jeske (2017). Mosby's Dental Drug Reference - E-Book. Elsevier Health Sciences. [ISBN:9780323511216]
  9. Kelsey J. and Marcus R. (2000). Menopause. Academic Press.
  10. NIH [Link]
  11. FDA approvals [Link]
  12. Pfizer [Link]
  13. Pfizer Safety Data Sheet [File]
External Links
KEGG Drug
D04070
PubChem Substance
46505680
ChemSpider
9532
ChEBI
8389
ChEMBL
CHEMBL2106240
Therapeutic Targets Database
DNC001150
PharmGKB
PA164754789
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Conjugated_estrogen
ATC Codes
G03CA57 — Conjugated estrogensG03CC07 — Conjugated estrogens and bazedoxifene
AHFS Codes
  • 68:16.04 — Estrogens
FDA label
Download (434 KB)
MSDS
Download (393 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionMenopause1
1CompletedNot AvailableAtrophic Vaginitis1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedDiagnosticEstrogen Replacement Therapy / Healthy Volunteers1
1CompletedHealth Services ResearchOne to five years postmenopausal1
1CompletedPreventionOne to five years postmenopausal1
1CompletedScreeningOne to five years postmenopausal1
1CompletedTreatmentOne to five years postmenopausal2
1, 2RecruitingTreatmentIschemia Reperfusion Injury1
2Active Not RecruitingPreventionCancer, Breast1
2Active Not RecruitingTreatmentDisseminated Sclerosis / Menopause1
2CompletedPreventionCardiovascular Disease (CVD) / Endometrial Hyperplasia / Heart Diseases / Menopausal Complaints / Menopause / Uterine Diseases1
2CompletedTreatmentAmenorrhea / One to five years postmenopausal1
2CompletedTreatmentEndometriosis1
2CompletedTreatmentEpilepsies / Menopause1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / One to five years postmenopausal / Pre-Hypertension1
2CompletedTreatmentMenopausal and Female Climacteric States / Menopausal Hot Flushes1
2CompletedTreatmentParkinson's Disease (PD)1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentShock, Hemorrhagic1
2CompletedTreatmentTraumatic Brain Injury (TBI)1
2CompletedTreatmentOne to five years postmenopausal2
2TerminatedTreatmentMenopause1
2, 3CompletedHealth Services ResearchCardiovascular Disease (CVD) / Coronary Arteriosclerosis / Coronary Heart Disease (CHD) / Heart Diseases1
2, 3CompletedTreatmentAnorexia Nervosa (AN)1
3CompletedOtherPostmenopausal Women1
3CompletedPreventionBone Diseases / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Heart Diseases / High Blood Pressure (Hypertension) / High Cholesterol / Myocardial Ischemia / One to five years postmenopausal / Osteoporosis / Thrombotic events1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Arteriosclerosis / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia / One to five years postmenopausal1
3CompletedSupportive CareCancer, Breast / Menopausal Hot Flushes / Menopausal Symptoms1
3CompletedTreatmentHormone Replacement Therapy1
3CompletedTreatmentMenopause / Osteoporosis1
3CompletedTreatmentOsteoporosis1
3CompletedTreatmentPelvic Organ Prolapse (POP) / Vulvovaginal Atrophy1
3TerminatedTreatmentEndometrial Cancers1
3TerminatedTreatmentSystemic Lupus Erythematosus (SLE)1
4CompletedNot AvailableOne to five years postmenopausal1
4CompletedBasic ScienceMenopause / Pelvic Organ Prolapse (POP)1
4CompletedPreventionBMI >30 kg/m2 / Glucose Homeostasis / Postmenopausal Syndrome1
4CompletedSupportive CareAtrophic Vaginitis / Endometrial Hyperplasia / Pelvic Organ Prolapse (POP)1
4CompletedTreatmentIncontinence / Nocturia / Urinary Bladder, Overactive1
4RecruitingBasic ScienceAtrophic Vaginitis / Menopause / Urinary Tract Infections, Recurrent1
4RecruitingBasic ScienceDepression / Perimenopausal Disorder1
4RecruitingOtherPelvic Floor Disorders1
4RecruitingTreatmentCystocele / Pelvic Floor Disorders / Pelvic Organ Prolapse (POP) / Urogenital Prolapse / Uterine Prolapse / Vaginal Prolapse / Vaginal Vault Prolapse1
4RecruitingTreatmentMicroscopic Hematuria1
4RecruitingTreatmentUrinary Bladder, Overactive1
4TerminatedTreatmentSexual Dysfunction, Physiological1
4Unknown StatusPreventionArteriosclerosis / Menopause1
4WithdrawnTreatmentEstrogens / General Surgery / Menopause / Pelvic Floor Disorders1
Not AvailableCompletedNot AvailableAbnormal Mammogram / Mammographic Density1
Not AvailableCompletedNot AvailableDementia Syndromes1
Not AvailableCompletedTreatmentAtrophic Vaginitis / Menopause1
Not AvailableCompletedTreatmentOvarian Failure, Premature1
Not AvailableCompletedTreatmentUnspecified Injury of Brachial Artery, Left Side, Initial Encounter1
Not AvailableCompletedTreatmentUrinary Bladder, Overactive1
Not AvailableEnrolling by InvitationNot AvailablePelvic Organ Prolapse (POP) / Postoperative pain1
Not AvailableRecruitingTreatmentPelvic Organ Prolapse (POP)1
Not AvailableTerminatedTreatmentMenopausal Hot Flushes1
Not AvailableUnknown StatusPreventionQuality of Life / Urinary Tract Infections (UTIs) / Vaginal Infections1
Not AvailableUnknown StatusSupportive CareCancer, Breast / Menopausal Hot Flushes / Menopausal Symptoms / Osteoporosis1

Pharmacoeconomics

Manufacturers
  • Wyeth pharmaceuticals inc
  • Duramed research inc
  • Teva womens health inc
  • Roche palo alto llc
Packagers
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Cardinal Health
  • Caremark LLC
  • Comprehensive Consultant Services Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Direct Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Duramed
  • Group Health Cooperative
  • H.E. Butt Grocery Co.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Mallinckrodt Inc.
  • Martin Surgical Supply
  • Mckesson Corp.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Noxzema Inc.
  • Nucare Pharmaceuticals Inc.
  • Patheon Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacy Service Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Primedics Laboratories
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Rite Aid Corp.
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Talbert Medical Management Corp.
  • Tya Pharmaceuticals
  • Vangard Labs Inc.
  • Wyeth Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral0.3 mg
TabletOral0.625 mg
TabletOral1.25 mg
TabletOral2.5 mg
Tablet, film coatedOral
Tablet, multilayer, extended releaseOral
TabletOral
CreamTopical; Vaginal0.625 mg/1g
Injection, powder, lyophilized, for solutionIntramuscular; Intravenous25 mg/5mL
Tablet, extended releaseOral0.3 mg
Tablet, extended releaseOral0.625 mg
Tablet, extended releaseOral1.25 mg
Tablet, film coatedOral0.3 mg/1
Tablet, film coatedOral0.45 mg/1
Tablet, film coatedOral0.625 mg/1
Tablet, film coatedOral0.9 mg/1
Tablet, film coatedOral1.25 mg/1
Tablet, film coatedOral2.5 mg/1
Tablet, sugar coatedOral0.3 mg/1
Tablet, sugar coatedOral0.45 mg/1
Tablet, sugar coatedOral0.625 mg/1
Tablet, sugar coatedOral0.9 mg/1
CreamTopical; Vaginal.625 mg
Powder, for solutionIntramuscular; Intravenous25 mg
TabletOral0.9 mg
CreamVaginal0.625 mg/1g
CreamVaginal0.625 mg
Kit
Kit; tabletOral
Tablet, sugar coatedOral
Prices
Unit descriptionCostUnit
Premarin 0.625 mg/gm Cream 42.5 gm Tube134.05USD tube
Premarin 25 mg vial107.54USD vial
Premphase 28 0.625-5 mg tablet Disp Pack69.99USD disp
Premarin vaginal cream-appl3.07USD g
Prempro 0.3 mg-1.5 mg tablet2.34USD tablet
Prempro 0.45-1.5 mg tablet2.34USD tablet
Prempro 0.625-2.5 mg tablet2.34USD tablet
Prempro 0.625-5 mg tablet2.34USD tablet
Premarin 0.45 mg tablet1.97USD tablet
Premarin 0.9 mg tablet1.97USD tablet
Premarin 2.5 mg tablet1.83USD tablet
Premarin 2.5 mg Tabs1.82USD tablet
Premarin 0.3 mg tablet1.42USD tablet
Premarin 0.625 mg tablet1.42USD tablet
Premarin 1.25 mg tablet1.42USD tablet
Premarin 0.625 mg/g Cream0.69USD g
C.E.S. 0.625 mg Tablet0.11USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5908638No1999-06-012015-07-26Us
US5547948No1996-08-202015-01-17Us
US5998402No1999-12-072017-04-04Us
US6479535No2002-11-122019-05-06Us
US7138392No2006-11-212017-04-04Us
US7683051No2010-03-232027-03-10Us
US8815934No2014-08-262019-05-06Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Can range from 173-282 °C depending of the componentReport on carcinogens. 12th edition. NIH.
water solubilitySoluble'MSDS'
logP3.7Hsieh R. et al. 2007. Steroids.
pKa10Hurwitz AR. and Liu ST. J Pharm Sci. 1977. (based on the average of different estrogens)
Predicted Properties
Not Available
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.997
Blood Brain Barrier+0.9486
Caco-2 permeable-0.8738
P-glycoprotein substrateNon-substrate0.5295
P-glycoprotein inhibitor INon-inhibitor0.5198
P-glycoprotein inhibitor IINon-inhibitor0.9431
Renal organic cation transporterNon-inhibitor0.8313
CYP450 2C9 substrateNon-substrate0.7886
CYP450 2D6 substrateNon-substrate0.8125
CYP450 3A4 substrateSubstrate0.6454
CYP450 1A2 substrateNon-inhibitor0.8152
CYP450 2C9 inhibitorNon-inhibitor0.8454
CYP450 2D6 inhibitorNon-inhibitor0.9026
CYP450 2C19 inhibitorNon-inhibitor0.8017
CYP450 3A4 inhibitorNon-inhibitor0.9204
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8461
Ames testNon AMES toxic0.5177
CarcinogenicityNon-carcinogens0.5338
BiodegradationNot ready biodegradable0.6303
Rat acute toxicity2.3418 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6053
hERG inhibition (predictor II)Inhibitor0.7941
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Ropero AB, Eghbali M, Minosyan TY, Tang G, Toro L, Stefani E: Heart estrogen receptor alpha: distinct membrane and nuclear distribution patterns and regulation by estrogen. J Mol Cell Cardiol. 2006 Sep;41(3):496-510. Epub 2006 Jul 28. [PubMed:16876190]
  2. Stroud FC, Appt SE, Wilson ME, Franke AA, Adams MR, Kaplan JR: Concentrations of isoflavones in macaques consuming standard laboratory monkey diet. J Am Assoc Lab Anim Sci. 2006 Jul;45(4):20-3. [PubMed:16884174]
  3. Hou NN, Zhu YM, Huang HF: [The expression of estrogen receptor alpha and beta in the intervention of different estrogens in rat bone metabolism]. Fen Zi Xi Bao Sheng Wu Xue Bao. 2006 Aug;39(4):289-96. [PubMed:16955786]
  4. Gouva L, Tsatsoulis A: The role of estrogens in cardiovascular disease in the aftermath of clinical trials. Hormones (Athens). 2004 Jul-Sep;3(3):171-83. [PubMed:16982590]
  5. Smith MR: Selective estrogen receptor modulators to prevent treatment-related osteoporosis. Rev Urol. 2005;7 Suppl 3:S30-5. [PubMed:16985877]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Cada DJ, Baker DE: Conjugated estrogens and bazedoxifene. Hosp Pharm. 2014 Mar;49(3):273-83. doi: 10.1310/hpj4903-273. [PubMed:24715748]
  2. Ropero AB, Eghbali M, Minosyan TY, Tang G, Toro L, Stefani E: Heart estrogen receptor alpha: distinct membrane and nuclear distribution patterns and regulation by estrogen. J Mol Cell Cardiol. 2006 Sep;41(3):496-510. Epub 2006 Jul 28. [PubMed:16876190]
  3. Stroud FC, Appt SE, Wilson ME, Franke AA, Adams MR, Kaplan JR: Concentrations of isoflavones in macaques consuming standard laboratory monkey diet. J Am Assoc Lab Anim Sci. 2006 Jul;45(4):20-3. [PubMed:16884174]
  4. Hou NN, Zhu YM, Huang HF: [The expression of estrogen receptor alpha and beta in the intervention of different estrogens in rat bone metabolism]. Fen Zi Xi Bao Sheng Wu Xue Bao. 2006 Aug;39(4):289-96. [PubMed:16955786]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT: Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98. [PubMed:12865317]
  2. Authors unspecified: Conjugated oestrogens/bazedoxifene. Aust Prescr. 2017 Jun;40(3):114-115. doi: 10.18773/austprescr.2017.039. Epub 2017 May 10. [PubMed:28798519]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Lin Y, Lu P, Tang C, Mei Q, Sandig G, Rodrigues AD, Rushmore TH, Shou M: Substrate inhibition kinetics for cytochrome P450-catalyzed reactions. Drug Metab Dispos. 2001 Apr;29(4 Pt 1):368-74. [PubMed:11259318]
  2. O'Connell MB, Frye RF, Matzke GR, St Peter JV, Willhite LA, Welch MR, Kowal P, LaValleur J: Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women. J Clin Pharmacol. 2006 Nov;46(11):1299-307. doi: 10.1177/0091270006292249. [PubMed:17050794]
  3. CTEP CYP1A2 DOCUMENT [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
O-methyltransferase activity
Specific Function
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOP...
Gene Name
COMT
Uniprot ID
P21964
Uniprot Name
Catechol O-methyltransferase
Molecular Weight
30036.77 Da
References
  1. Zhu BT, Wu KY, Wang P, Cai MX, Conney AH: O-methylation of catechol estrogens by human placental catechol-o-methyltransferase: interindividual differences in sensitivity to heat inactivation and to inhibition by dietary polyphenols. Drug Metab Dispos. 2010 Oct;38(10):1892-9. doi: 10.1124/dmd.110.033548. Epub 2010 Jul 6. [PubMed:20606002]
  2. Jobe SO, Ramadoss J, Koch JM, Jiang Y, Zheng J, Magness RR: Estradiol-17beta and its cytochrome P450- and catechol-O-methyltransferase-derived metabolites stimulate proliferation in uterine artery endothelial cells: role of estrogen receptor-alpha versus estrogen receptor-beta. Hypertension. 2010 Apr;55(4):1005-11. doi: 10.1161/HYPERTENSIONAHA.109.146399. Epub 2010 Mar 8. [PubMed:20212268]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. CYTOMEL (liothyronine) FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Cada DJ, Baker DE: Conjugated estrogens and bazedoxifene. Hosp Pharm. 2014 Mar;49(3):273-83. doi: 10.1310/hpj4903-273. [PubMed:24715748]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Cada DJ, Baker DE: Conjugated estrogens and bazedoxifene. Hosp Pharm. 2014 Mar;49(3):273-83. doi: 10.1310/hpj4903-273. [PubMed:24715748]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. Hirohashi T, Suzuki H, Sugiyama Y: Characterization of the transport properties of cloned rat multidrug resistance-associated protein 3 (MRP3). J Biol Chem. 1999 May 21;274(21):15181-5. [PubMed:10329726]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Zelcer N, Reid G, Wielinga P, Kuil A, van der Heijden I, Schuetz JD, Borst P: Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7. [PubMed:12523936]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Qian YM, Song WC, Cui H, Cole SP, Deeley RG: Glutathione stimulates sulfated estrogen transport by multidrug resistance protein 1. J Biol Chem. 2001 Mar 2;276(9):6404-11. Epub 2000 Dec 1. [PubMed:11102445]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Gao B, Hagenbuch B, Kullak-Ublick GA, Benke D, Aguzzi A, Meier PJ: Organic anion-transporting polypeptides mediate transport of opioid peptides across blood-brain barrier. J Pharmacol Exp Ther. 2000 Jul;294(1):73-9. [PubMed:10871297]
  2. Kullak-Ublick GA, Fisch T, Oswald M, Hagenbuch B, Meier PJ, Beuers U, Paumgartner G: Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in human liver and brain. FEBS Lett. 1998 Mar 13;424(3):173-6. [PubMed:9539145]
  3. Kanai N, Lu R, Bao Y, Wolkoff AW, Vore M, Schuster VL: Estradiol 17 beta-D-glucuronide is a high-affinity substrate for oatp organic anion transporter. Am J Physiol. 1996 Feb;270(2 Pt 2):F326-31. [PubMed:8779894]
  4. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. [PubMed:8786566]
  5. Kontaxi M, Echkardt U, Hagenbuch B, Stieger B, Meier PJ, Petzinger E: Uptake of the mycotoxin ochratoxin A in liver cells occurs via the cloned organic anion transporting polypeptide. J Pharmacol Exp Ther. 1996 Dec;279(3):1507-13. [PubMed:8968376]
  6. Pang KS, Wang PJ, Chung AY, Wolkoff AW: The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein. Hepatology. 1998 Nov;28(5):1341-6. [PubMed:9794920]
  7. Bossuyt X, Muller M, Meier PJ: Multispecific amphipathic substrate transport by an organic anion transporter of human liver. J Hepatol. 1996 Nov;25(5):733-8. [PubMed:8938553]
  8. Hagenbuch B, Adler ID, Schmid TE: Molecular cloning and functional characterization of the mouse organic-anion-transporting polypeptide 1 (Oatp1) and mapping of the gene to chromosome X. Biochem J. 2000 Jan 1;345 Pt 1:115-20. [PubMed:10600646]
  9. Lee TK, Koh AS, Cui Z, Pierce RH, Ballatori N: N-glycosylation controls functional activity of Oatp1, an organic anion transporter. Am J Physiol Gastrointest Liver Physiol. 2003 Aug;285(2):G371-81. Epub 2003 Apr 17. [PubMed:12702494]
  10. Kouzuki H, Suzuki H, Ito K, Ohashi R, Sugiyama Y: Contribution of organic anion transporting polypeptide to uptake of its possible substrates into rat hepatocytes. J Pharmacol Exp Ther. 1999 Feb;288(2):627-34. [PubMed:9918568]
  11. Eckhardt U, Schroeder A, Stieger B, Hochli M, Landmann L, Tynes R, Meier PJ, Hagenbuch B: Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in stably transfected CHO cells. Am J Physiol. 1999 Apr;276(4 Pt 1):G1037-42. [PubMed:10198348]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Schroeder A, Eckhardt U, Stieger B, Tynes R, Schteingart CD, Hofmann AF, Meier PJ, Hagenbuch B: Substrate specificity of the rat liver Na(+)-bile salt cotransporter in Xenopus laevis oocytes and in CHO cells. Am J Physiol. 1998 Feb;274(2 Pt 1):G370-5. [PubMed:9486191]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Not Available
Gene Name
SLC22A10
Uniprot ID
Q63ZE4
Uniprot Name
Solute carrier family 22 member 10
Molecular Weight
60256.57 Da
References
  1. Youngblood GL, Sweet DH: Identification and functional assessment of the novel murine organic anion transporter Oat5 (Slc22a19) expressed in kidney. Am J Physiol Renal Physiol. 2004 Aug;287(2):F236-44. Epub 2004 Apr 6. [PubMed:15068970]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [PubMed:14762099]
  2. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T: Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab. 2003 Apr;23(4):432-40. [PubMed:12679720]
  3. Nagata Y, Kusuhara H, Endou H, Sugiyama Y: Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002 May;61(5):982-8. [PubMed:11961115]
  4. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713]
  5. Sweet DH, Miller DS, Pritchard JB, Fujiwara Y, Beier DR, Nigam SK: Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice. J Biol Chem. 2002 Jul 26;277(30):26934-43. Epub 2002 May 13. [PubMed:12011098]
  6. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. [PubMed:15100168]
  7. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. [PubMed:10224140]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-gluc...
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
References
  1. Tohyama K, Kusuhara H, Sugiyama Y: Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology. 2004 Sep;145(9):4384-91. Epub 2004 May 27. [PubMed:15166123]
  2. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [PubMed:12351693]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A: Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm Res. 2001 Sep;18(9):1262-9. [PubMed:11683238]
  2. Nozawa T, Tamai I, Sai Y, Nezu J, Tsuji A: Contribution of organic anion transporting polypeptide OATP-C to hepatic elimination of the opioid pentapeptide analogue [D-Ala2, D-Leu5]-enkephalin. J Pharm Pharmacol. 2003 Jul;55(7):1013-20. [PubMed:12906759]
  3. Cui Y, Konig J, Leier I, Buchholz U, Keppler D: Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem. 2001 Mar 30;276(13):9626-30. Epub 2000 Dec 27. [PubMed:11134001]
  4. Hirano M, Maeda K, Shitara Y, Sugiyama Y: Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J Pharmacol Exp Ther. 2004 Oct;311(1):139-46. Epub 2004 May 24. [PubMed:15159445]
  5. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. [PubMed:14977862]
  6. Matsushima S, Maeda K, Kondo C, Hirano M, Sasaki M, Suzuki H, Sugiyama Y: Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther. 2005 Sep;314(3):1059-67. Epub 2005 May 18. [PubMed:15901800]
  7. van Montfoort JE, Schmid TE, Adler ID, Meier PJ, Hagenbuch B: Functional characterization of the mouse organic-anion-transporting polypeptide 2. Biochim Biophys Acta. 2002 Aug 19;1564(1):183-8. [PubMed:12101011]
  8. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
  2. Tamai I, Nozawa T, Koshida M, Nezu J, Sai Y, Tsuji A: Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C. Pharm Res. 2001 Sep;18(9):1262-9. [PubMed:11683238]
  3. Kobayashi D, Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I: Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther. 2003 Aug;306(2):703-8. Epub 2003 Apr 30. [PubMed:12724351]
  4. Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I: Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45. Epub 2003 Nov 10. [PubMed:14610227]
  5. Satoh H, Yamashita F, Tsujimoto M, Murakami H, Koyabu N, Ohtani H, Sawada Y: Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005 Apr;33(4):518-23. Epub 2005 Jan 7. [PubMed:15640378]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Matsushima S, Maeda K, Kondo C, Hirano M, Sasaki M, Suzuki H, Sugiyama Y: Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther. 2005 Sep;314(3):1059-67. Epub 2005 May 18. [PubMed:15901800]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Sweet DH, Miller DS, Pritchard JB, Fujiwara Y, Beier DR, Nigam SK: Impaired organic anion transport in kidney and choroid plexus of organic anion transporter 3 (Oat3 (Slc22a8)) knockout mice. J Biol Chem. 2002 Jul 26;277(30):26934-43. Epub 2002 May 13. [PubMed:12011098]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood. Efficie...
Gene Name
SLC51A
Uniprot ID
Q86UW1
Uniprot Name
Organic solute transporter subunit alpha
Molecular Weight
37734.575 Da
References
  1. Seward DJ, Koh AS, Boyer JL, Ballatori N: Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82. Epub 2003 Apr 28. [PubMed:12719432]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood. Efficie...
Gene Name
SLC51B
Uniprot ID
Q86UW2
Uniprot Name
Organic solute transporter subunit beta
Molecular Weight
14346.195 Da
References
  1. Seward DJ, Koh AS, Boyer JL, Ballatori N: Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta. J Biol Chem. 2003 Jul 25;278(30):27473-82. Epub 2003 Apr 28. [PubMed:12719432]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Spears KJ, Ross J, Stenhouse A, Ward CJ, Goh LB, Wolf CR, Morgan P, Ayrton A, Friedberg TH: Directional trans-epithelial transport of organic anions in porcine LLC-PK1 cells that co-express human OATP1B1 (OATP-C) and MRP2. Biochem Pharmacol. 2005 Feb 1;69(3):415-23. Epub 2004 Dec 22. [PubMed:15652233]
  2. Matsushima S, Maeda K, Kondo C, Hirano M, Sasaki M, Suzuki H, Sugiyama Y: Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther. 2005 Sep;314(3):1059-67. Epub 2005 May 18. [PubMed:15901800]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate.
Gene Name
SLCO4A1
Uniprot ID
Q96BD0
Uniprot Name
Solute carrier organic anion transporter family member 4A1
Molecular Weight
77192.505 Da
References
  1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. [PubMed:10873595]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Purine nucleotide transmembrane transporter activity
Specific Function
Participates in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides. Enhances the cellular extrusion of cAMP and cGMP. Stimulates the ATP-dependent uptake of a ...
Gene Name
ABCC11
Uniprot ID
Q96J66
Uniprot Name
ATP-binding cassette sub-family C member 11
Molecular Weight
154299.625 Da
References
  1. Chen ZS, Guo Y, Belinsky MG, Kotova E, Kruh GD: Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005 Feb;67(2):545-57. Epub 2004 Nov 10. [PubMed:15537867]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Cui Y, Konig J, Leier I, Buchholz U, Keppler D: Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem. 2001 Mar 30;276(13):9626-30. Epub 2000 Dec 27. [PubMed:11134001]
  2. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [PubMed:11159893]
  3. Hirano M, Maeda K, Shitara Y, Sugiyama Y: Contribution of OATP2 (OATP1B1) and OATP8 (OATP1B3) to the hepatic uptake of pitavastatin in humans. J Pharmacol Exp Ther. 2004 Oct;311(1):139-46. Epub 2004 May 24. [PubMed:15159445]
  4. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. [PubMed:14977862]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. [PubMed:10660625]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as estrone-3-sulfate (PubMed:10873595). Mediates transport of prostaglandins (PG) E1 and E2, thyroxine (T4), deltorphin II, BQ-123 an...
Gene Name
SLCO3A1
Uniprot ID
Q9UIG8
Uniprot Name
Solute carrier organic anion transporter family member 3A1
Molecular Weight
76552.135 Da
References
  1. Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, Tsuji A: Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun. 2000 Jun 24;273(1):251-60. [PubMed:10873595]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Matsushima S, Maeda K, Kondo C, Hirano M, Sasaki M, Suzuki H, Sugiyama Y: Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther. 2005 Sep;314(3):1059-67. Epub 2005 May 18. [PubMed:15901800]
  2. Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y: ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 2003 Jun 20;278(25):22644-9. Epub 2003 Apr 7. [PubMed:12682043]
  3. Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y: Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol. 2003 Sep;64(3):610-8. [PubMed:12920197]

Drug created on June 13, 2005 07:24 / Updated on April 19, 2019 18:57