Identification

Name
Lutropin alfa
Accession Number
DB00044  (BTD00056, BIOD00056)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Description

Lutropin alfa is a recombinant human luteinizing hormone produced in yeast with 2 subunits, alpha = 92 residues, beta = 121 residues. It is a heterodimeric glycoprotein. Each monomeric unit is a glycoprotein molecule. In females, an acute rise of LH ("LH surge") triggers ovulation and the development of the corpus luteum. In males, it stimulates Leydig cell production of testosterone. Lutropin alfa was the first and only recombinant human form of luteinizing hormone (LH) developed for use in the stimulation of follicular development.

Protein structure
Db00044
Protein chemical formula
C1014H1609N287O294S27
Protein average weight
30000.0 Da
Sequences
>Alpha Chain
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCC
VAKSYNRVTVMGGFKVENHTACHCSTCYYHKS
>Beta Chain (LH)
SREPLRPWCHPINAILAVEKEGCPVCITVNTTICAGYCPTMMRVLQAVLPPLPQVVCTYR
DVRFESIRLPGCPRGVDPVVSFPVALSCRCGPCRRSTSDCGGPKDHPLTCDHPQLSGLLF
L
Download FASTA Format
Synonyms
  • ICSH
  • Insterstiial cell-stimulating hormone
  • LH
  • LH-B
  • LSH- beta
  • LSH-B
  • Luteinizing hormone
  • Luteinizing hormone beta subunit
  • Lutrophin
  • Lutropin alpha
  • Lutropin beta chain precursor
  • Lutropina alfa
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LuverisPowder, for solution75 unitSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2005-06-28Not applicableCanada
LuverisKit82.5 [iU]/1mLSubcutaneousEmd Serono2004-10-082014-11-30Us
LuverisSolution450 unitSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Humegon Inj 75 I.U.Lutropin alfa (75 unit) + Follitropin (75 unit) + Sodium Chloride (.9 %)Liquid; Powder, for solutionIntramuscularOrganon Canada Ltd Ltee1993-12-312006-08-17Canada
MenopurLutropin alfa (75 [iU]/1mL) + Follitropin (75 [iU]/1mL) + Sodium Chloride (9 mg/1mL)KitFerring Pharmaceuticals2004-10-29Not applicableUs
Pergonal 75 I.U.Lutropin alfa (75 unit) + Follitropin (75 unit)Powder, for solutionIntramuscularEmd Serono, A Division Of Emd Inc., Canada1979-12-312007-05-07Canada
PergoverisLutropin alfa (450 unit) + Follitropin (900 unit)SolutionSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada
PergoverisLutropin alfa (75 unit) + Follitropin (150 unit)Kit; Powder, for solutionSubcutaneousEmd Serono, A Division Of Emd Inc., Canada2015-10-22Not applicableCanada
PergoverisLutropin alfa (75 IU r-hLH) + Follitropin (150 IU r-hFSH)Injection, powder, for solutionSubcutaneousMerck Serono Europe Limited2007-06-25Not applicableEu
PergoverisLutropin alfa (225 unit) + Follitropin (450 unit)SolutionSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada
PergoverisLutropin alfa (75 IU r-hLH) + Follitropin (150 IU r-hFSH)Injection, powder, for solutionSubcutaneousMerck Serono Europe Limited2007-06-25Not applicableEu
PergoverisLutropin alfa (150 unit) + Follitropin (300 unit)SolutionSubcutaneousEmd Serono, A Division Of Emd Inc., CanadaNot applicableNot applicableCanada
PergoverisLutropin alfa (75 IU r-hLH) + Follitropin (150 IU r-hFSH)Injection, powder, for solutionSubcutaneousMerck Serono Europe Limited2007-06-25Not applicableEu
Categories
UNII
3JGY52XJNA
CAS number
152923-57-4

Pharmacology

Indication

For treatment of infertility in women with hypothalamic or pituitary insufficiency (hypogonadotropic hypogonadism) and profound LH deficiency (LH <1.2 international units [IU]/L)

Associated Conditions
Pharmacodynamics

Used to facilitate female conception, lutropin alfa performs the same actions as luteinizing hormone (LH), which is normally produced in the pituitary gland. Lutropin is usually given in combination with follitropin alfa. Together they stimulate the development of a follicle to prepare the reproductive tract for implementation and pregnancy. Lutropin alfa also stimulates the theca cells to produce androgens and the secretion of estradiol by the follicles. Lutropin alfa and follitropin alfa are discontinued once ultrasound assessment and serum estradiol concentrations show sufficient follicular maturation. hCG is then administered to complete follicular maturation and induce ovulation. In females, a LH surge about halfway through the menstrual cycle triggers the onset of ovulation. Lutropin alfa substitutes for endogenous LH and induces rupture of the preovulatory ovarian follicle and oocyte expulsion. Lutropin alfa induces and maintains the corpus luteum, which then secretes progesterone.

Mechanism of action

Luteinizing hormone binds to a receptor shared with the human chorionic gonadotropin hormone (hCG) on the ovarian theca (and granulosa) cells and testicular Leydig cells. This LH/CG transmembrane receptor is a member of the super-family of G protein-coupled receptors. Adenylate cyclase then activates many other pathways leading to steroid hormone production and other follicle maturation processes.

TargetActionsOrganism
ALutropin-choriogonadotropic hormone receptor
agonist
Human
Absorption

Mean absolute bioavailability is 56%, following sub-Q administration, maximum serum concentrations reached after 4–16 hours. Time to peak, serum: 9 hours

Volume of distribution

The steady state volume of distribution is around 10-14 L.

Protein binding
Not Available
Metabolism

<5% of dose excreted renally as unchanged drug.

Route of elimination

Total body clearance is approximately 2 to 3 L/h with less than 5 percent of the dose being excreted unchanged renally.

Half life

Biphasic; terminal half-life is approximately 18 hours.

Clearance
  • 2 – 3 L/h [healthy female following subcutaneous administration]
Toxicity

Lutropin alfa is not indicated for people under 16 and over 60, pregnant and lactating women, patients with uncontrolled thyroid and adrenal failure, patients with active, untreated tumours of the hypothalamus and pituitary gland, and in any patient with a condition that makes a normal pregnancy possible such as primary ovarian failure or fibroid tumors of the uterus.

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

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
  1. Blanchard J: Gastrointestinal absorption. I. Mechanisms. Am J Pharm Sci Support Public Health. 1975 Sep-Oct;147(5):135-46. [PubMed:3972]
  2. Louvet JP, Harman SM, Ross GT: Effects of human chorionic gonadotropin, human interstitial cell stimulating hormone and human follicle-stimulating hormone on ovarian weights in estrogen-primed hypophysectomized immature female rats. Endocrinology. 1975 May;96(5):1179-86. [PubMed:1122882]
  3. Nielsen MS, Barton SD, Hatasaka HH, Stanford JB: Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick. Fertil Steril. 2001 Aug;76(2):384-7. [PubMed:11476792]
  4. Gibreel A, Bhattacharya S: Recombinant follitropin alfa/lutropin alfa in fertility treatment. Biologics. 2010 Feb 4;4:5-17. [PubMed:20161981]
  5. Dhillon S, Keating GM: Lutropin alfa. Drugs. 2008;68(11):1529-40. [PubMed:18627209]
  6. Link [Link]
External Links
UniProt
P01229
Genbank
X00264
PubChem Substance
46507624
ChEMBL
CHEMBL1201419
Therapeutic Targets Database
DAP001103
PharmGKB
PA164750539
Drugs.com
Drugs.com Drug Page
Wikipedia
Lutropin_alfa
ATC Codes
G03GA07 — Lutropin alfa
AHFS Codes
  • 68:18.00 — Gonadotropins
FDA label
Download (218 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingBasic ScienceSleep Restriction1
2CompletedTreatmentInfertilities / Ovulation induction therapy1
2TerminatedTreatmentInfertilities / Ovulation induction therapy2
2Unknown StatusTreatmentInfertilities1
3CompletedTreatmentAssisted Reproductive Techniques / Reproductive Technology, Assisted1
3CompletedTreatmentHypogonadism1
3CompletedTreatmentInfertilities2
3CompletedTreatmentInfertilities / Ovarian Stimulation1
3TerminatedSupportive CareFertility / Follicle Stimulating Hormone Deficiency / Infertilities1
4CompletedPreventionInfertilities1
4CompletedTreatmentAssisted Reproductive Technology therapy / Infertilities1
4CompletedTreatmentInfertilities1
4CompletedTreatmentInfertility, Female Infertility, Male Infertility1
4CompletedTreatmentPregnancy1
4Not Yet RecruitingTreatmentInfertility, Female1
4RecruitingTreatmentIn Vitro Fertilisation / Infertility, Female / Ovarian Stimulation1
4RecruitingTreatmentInfertility, Female1
4TerminatedTreatmentIdiopathic Hypogonadotropic Hypogonadism1
4Unknown StatusTreatmentInfertilities1
Not AvailableCompletedNot AvailableBMI >30 kg/m21
Not AvailableCompletedScreeningOther Diseases or Conditions1
Not AvailableCompletedTreatmentIdiopathic Hypogonadotropic Hypogonadism1
Not AvailableCompletedTreatmentInfertilities1
Not AvailableCompletedTreatmentOutcome During r-hFSH and r-hLH Stimulation / Outcome During r-hFSH Stimulation1
Not AvailableUnknown StatusTreatmentComplications Associated With Artificial Fertilization / Female Infertility Due to Nonimplantation of Ovum1

Pharmacoeconomics

Manufacturers
  • Emd serono inc
Packagers
  • EMD Canada Inc.
  • Merck Serono SPA
Dosage forms
FormRouteStrength
Liquid; powder, for solutionIntramuscular
KitSubcutaneous82.5 [iU]/1mL
Powder, for solutionSubcutaneous75 unit
SolutionSubcutaneous450 unit
Kit
Powder, for solutionIntramuscular
Injection, powder, for solutionSubcutaneous
Kit; powder, for solutionSubcutaneous
SolutionSubcutaneous
KitIntramuscular; Subcutaneous
Prices
Unit descriptionCostUnit
Luveris 75 unit vial38.88USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5767251No1995-06-162015-06-16Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)55 °CForastieri, H., Ingham, K.C. J. Biol. Chem. 257:7976-7981 (1982)
hydrophobicity-0.063Not Available
isoelectric point8.44Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Luteinizing hormone receptor activity
Specific Function
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Gene Name
LHCGR
Uniprot ID
P22888
Uniprot Name
Lutropin-choriogonadotropic hormone receptor
Molecular Weight
78642.01 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Gibreel A, Bhattacharya S: Recombinant follitropin alfa/lutropin alfa in fertility treatment. Biologics. 2010 Feb 4;4:5-17. [PubMed:20161981]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:38