Identification

Name
Pyrimethamine
Accession Number
DB00205  (APRD00599)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.

Structure
Thumb
Synonyms
  • 2,4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidine
  • 2,4-Diamino-5-(P-chlorophenyl)-6-ethylpyrimidine
  • 2,4-Diamino-5-chlorophenyl-6-ethylpyrimidine
  • 5-(4-Chlorophenyl)-6-ethyl-2,4-diaminopyrimidine
  • 5-(4-Chlorophenyl)-6-ethyl-2,4-pyrimidinediamine
  • 5-(4'-Chlorophenyl)-2,4-diamino-6-ethylpyrimidine
  • CD
  • Chloridine
  • Chloridyn
  • Diaminopyritamin
  • Ethylpyrimidine
  • Pirimetamina
  • Primethamine
  • Pyriméthamine
  • Pyrimethaminum
External IDs
NSC-3061 / RP-4753 / WR-2978
Product Ingredients
IngredientUNIICASInChI Key
Pyrimethamine hydrochlorideNot Available19085-09-7JZCLIFPQURTYFA-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DaraprimTablet25 mg/1OralPhysicians Total Care, Inc.1994-05-122011-06-30Us
DaraprimTablet25 mgOralAmedra Pharmaceuticals LLC1952-12-312013-06-01Canada
DaraprimTablet25 mg/1OralAmedra Pharmaceuticals LLC1953-01-232016-10-31Us
DaraprimTablet25 mg/1OralKaiser Foundations Hospitals2011-04-20Not applicableUs
DaraprimTablet25 mg/1OralRemedy Repack2013-02-262014-02-27Us
DaraprimTablet25 mg/1OralGlaxosmithkline Inc1985-04-162013-03-31Us
DaraprimTablet25 mg/1OralVyera Pharmaceuticals Llc1953-01-23Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
FansidarPyrimethamine (25 mg/1) + Sulfadoxine (500 mg/1)TabletOralGenentech, Inc.1981-10-282012-04-18Us
Fansidar TabletsPyrimethamine (25 mg) + Sulfadoxine (500 mg)TabletOralHoffmann La Roche1989-12-312000-07-27Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Pyrimethamine LeucovorinPyrimethamine (50 mg/1) + Leucovorin calcium (20 min/1)CapsuleOralSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding2015-11-25Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (25 mg/1) + Leucovorin calcium (10 mg/1)CapsuleOralSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding2015-11-25Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (50 mg/1) + Leucovorin calcium (25 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (50 mg/1) + Leucovorin calcium (25 mg/1)CapsuleOralSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding2015-11-30Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (25 mg/1) + Leucovorin calcium (5 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (12.5 mg/1) + Leucovorin calcium (2.5 mg/1)CapsuleOralSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding2015-11-25Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (50 mg/1) + Leucovorin calcium (20 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (12.5 mg/1) + Leucovorin calcium (2.5 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (25 mg/1) + Leucovorin calcium (10 mg/1)CapsuleOralImprimisRx PA, Inc. d/b/a ImprimisRx2015-11-27Not applicableUs
Pyrimethamine LeucovorinPyrimethamine (25 mg/1) + Leucovorin calcium (5 mg/1)CapsuleOralSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding2015-11-25Not applicableUs
Categories
UNII
Z3614QOX8W
CAS number
58-14-0
Weight
Average: 248.711
Monoisotopic: 248.082874143
Chemical Formula
C12H13ClN4
InChI Key
WKSAUQYGYAYLPV-UHFFFAOYSA-N
InChI
InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
IUPAC Name
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
SMILES
CCC1=C(C(N)=NC(N)=N1)C1=CC=C(Cl)C=C1

Pharmacology

Indication

For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine

Associated Conditions
Pharmacodynamics

Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

Mechanism of action

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.

TargetActionsOrganism
ADihydrofolate reductase
inhibitor
Human
ABifunctional dihydrofolate reductase-thymidylate synthase
inhibitor
Plasmodium falciparum (isolate K1 / Thailand)
UBeta-hexosaminidase subunit betaNot AvailableHuman
Absorption

Well absorbed with peak levels occurring between 2 to 6 hours following administration

Volume of distribution
Not Available
Protein binding

87%

Metabolism

Hepatic

Route of elimination
Not Available
Half life

96 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Plasmodium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(6R)-Folinic acidThe therapeutic efficacy of Pyrimethamine can be decreased when used in combination with (6R)-Folinic acid.
(6S)-5,6,7,8-tetrahydrofolateThe therapeutic efficacy of Pyrimethamine can be decreased when used in combination with (6S)-5,6,7,8-tetrahydrofolate.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Pyrimethamine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Pyrimethamine.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Pyrimethamine.
AcepromazineThe risk or severity of QTc prolongation can be increased when Pyrimethamine is combined with Acepromazine.
AceprometazineThe risk or severity of QTc prolongation can be increased when Pyrimethamine is combined with Aceprometazine.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Pyrimethamine.
AcetophenazineThe risk or severity of QTc prolongation can be increased when Pyrimethamine is combined with Acetophenazine.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Pyrimethamine.
Food Interactions
  • Folic acid needs increased.
  • Take with food to reduce irritation.

References

Synthesis Reference
US2576939
General References
  1. Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. [PubMed:15155209]
  2. Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. [PubMed:14711307]
External Links
Human Metabolome Database
HMDB0014350
KEGG Drug
D00488
KEGG Compound
C07391
PubChem Compound
4993
PubChem Substance
46505987
ChemSpider
4819
BindingDB
18512
ChEBI
8673
ChEMBL
CHEMBL36
Therapeutic Targets Database
DAP000633
PharmGKB
PA451193
HET
CP6
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pyrimethamine
ATC Codes
P01BF04 — Artesunate, sulphamethopyrazine and pyrimethamineP01BD01 — PyrimethamineP01BD51 — Pyrimethamine, combinations
PDB Entries
1j3j / 2bl9 / 2bla / 3lmy / 3qfx / 3qg2 / 3qgt / 3um5 / 4km0 / 6aog
FDA label
Download (29.7 KB)
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionPlasmodium Infections1
1CompletedTreatmentAutoimmune Diseases / Lymphatic Diseases / Lymphoproliferative Disorders1
1CompletedTreatmentAutoimmune Diseases / Lymphoproliferative Disorders1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral2
1CompletedTreatmentToxoplasmosis1
1Not Yet RecruitingTreatmentMyelodysplastic Syndromes1
1RecruitingPreventionPlasmodium Infections1
1WithdrawnNot AvailableG(M2) Ganglioside / Sandhoff Disease Ganglioside / Tay-Sachs Disease Ganglioside1
1, 2CompletedTreatmentFamilial Amyotrophic Lateral Sclerosis1
1, 2CompletedTreatmentGangliosidoses, GM2 / Sandhoff Disease / Tay-Sachs Disease1
1, 2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Small Lymphocytic1
1, 2RecruitingTreatmentHIV-1-infection1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
2, 3CompletedPreventionPlasmodium Infections1
2, 3CompletedTreatmentPlasmodium Infections1
3Active Not RecruitingPreventionPlasmodium Infections / Pregnancy1
3CompletedPreventionPlasmodium Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii1
3CompletedTreatmentMajor Depressive Disorder (MDD) / Schizophrenic Disorders1
3CompletedTreatmentPlasmodium Infections1
3CompletedTreatmentSchistosoma Mansoni1
3CompletedTreatmentToxoplasmosis, Congenital1
3TerminatedTreatmentPlasmodium Infections1
3WithdrawnTreatmentPlasmodium Falciparum Malaria1
4CompletedPreventionPlasmodium Infections1
4CompletedTreatmentPlasmodium Falciparum Malaria / Plasmodium Infections1
4RecruitingTreatmentToxoplasmosis1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral2
Not AvailableCompletedTreatmentMalaria caused by Plasmodium falciparum / Malaria caused by plasmodium vivax1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline llc
Packagers
  • DSM Corp.
  • GlaxoSmithKline Inc.
  • Kaiser Foundation Hospital
  • Medisca Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral25 mg
TabletOral25 mg/1
TabletOral
CapsuleOral
Prices
Unit descriptionCostUnit
Pyrimethamine powder8.88USD g
Daraprim 25 mg tablet0.98USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)233.5 °CPhysProp
water solubility121 mg/LNot Available
logP2.69HANSCH,C ET AL. (1995)
pKa7.34 (at 20 °C)PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility0.179 mg/mLALOGPS
logP2.62ALOGPS
logP2.75ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)17.22ChemAxon
pKa (Strongest Basic)7.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area77.82 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.54 m3·mol-1ChemAxon
Polarizability25.79 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9973
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6217
P-glycoprotein substrateNon-substrate0.5822
P-glycoprotein inhibitor INon-inhibitor0.8643
P-glycoprotein inhibitor IINon-inhibitor0.9045
Renal organic cation transporterNon-inhibitor0.7451
CYP450 2C9 substrateNon-substrate0.8103
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6582
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.7586
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6667
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8016
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7833 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9337
hERG inhibition (predictor II)Non-inhibitor0.8586
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - CI-BGC-MSsplash10-0002-0090000000-4e966bed391e234a23e3
Mass Spectrum (Electron Ionization)MSsplash10-0002-2590000000-6434b6f0181741b3ca41
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0090000000-a146b85d59fc9835ed4c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0090000000-84e4cea277c64351f21b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0190000000-d931593de00f33f04587
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0059-0980000000-a232e355dd50976aea07
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-005a-0920000000-7d48f7cfecbd7823803a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0290000000-b6d3f56ade24c0e6984c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0290000000-415b60a9caab352df184
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0032-2960000000-583d00b81182f34e5a94

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminopyrimidines and derivatives. These are organic compounds containing an amino group attached to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Aminopyrimidines and derivatives
Alternative Parents
Chlorobenzenes / Hydropyrimidines / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Aminopyrimidine / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Hydropyrimidine / Benzenoid / Heteroaromatic compound / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aminopyrimidine, monochlorobenzenes (CHEBI:8673)

Targets

Details
1. Dihydrofolate reductase
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadph binding
Specific Function
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA pre...
Gene Name
DHFR
Uniprot ID
P00374
Uniprot Name
Dihydrofolate reductase
Molecular Weight
21452.61 Da
References
  1. Rastelli G, Pacchioni S, Parenti MD: Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3257-60. [PubMed:12951104]
  2. Fidock DA, Wellems TE: Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6. [PubMed:9380737]
  3. Wooden JM, Hartwell LH, Vasquez B, Sibley CH: Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum. Mol Biochem Parasitol. 1997 Mar;85(1):25-40. [PubMed:9108546]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Thymidylate synthase activity
Specific Function
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and f...
Gene Name
Not Available
Uniprot ID
P13922
Uniprot Name
Bifunctional dihydrofolate reductase-thymidylate synthase
Molecular Weight
71816.775 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. Fohl LM, Roos DS: Fitness effects of DHFR-TS mutations associated with pyrimethamine resistance in apicomplexan parasites. Mol Microbiol. 2003 Nov;50(4):1319-27. [PubMed:14622418]
  4. McKie JH, Douglas KT, Chan C, Roser SA, Yates R, Read M, Hyde JE, Dascombe MJ, Yuthavong Y, Sirawaraporn W: Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria. J Med Chem. 1998 Apr 23;41(9):1367-70. [PubMed:9554869]
  5. Zolg JW, Plitt JR, Chen GX, Palmer S: Point mutations in the dihydrofolate reductase-thymidylate synthase gene as the molecular basis for pyrimethamine resistance in Plasmodium falciparum. Mol Biochem Parasitol. 1989 Oct;36(3):253-62. [PubMed:2677719]
  6. Zhang K, Rathod PK: Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science. 2002 Apr 19;296(5567):545-7. [PubMed:11964483]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Protein homodimerization activity
Specific Function
Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
Gene Name
HEXB
Uniprot ID
P07686
Uniprot Name
Beta-hexosaminidase subunit beta
Molecular Weight
63110.745 Da
References
  1. Bateman KS, Cherney MM, Mahuran DJ, Tropak M, James MN: Crystal structure of beta-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone. J Med Chem. 2011 Mar 10;54(5):1421-9. doi: 10.1021/jm101443u. Epub 2011 Jan 25. [PubMed:21265544]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Oh J, Chung H, Park SI, Yi SJ, Jang K, Kim AH, Yoon J, Cho JY, Yoon SH, Jang IJ, Yu KS, Chung JY: Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans. Diabetes Obes Metab. 2016 Jan;18(1):104-8. doi: 10.1111/dom.12577. Epub 2015 Oct 26. [PubMed:26381793]
  2. Kusuhara H, Ito S, Kumagai Y, Jiang M, Shiroshita T, Moriyama Y, Inoue K, Yuasa H, Sugiyama Y: Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther. 2011 Jun;89(6):837-44. doi: 10.1038/clpt.2011.36. Epub 2011 May 4. [PubMed:21544077]
  3. May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [PubMed:27092232]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. Oh J, Chung H, Park SI, Yi SJ, Jang K, Kim AH, Yoon J, Cho JY, Yoon SH, Jang IJ, Yu KS, Chung JY: Inhibition of the multidrug and toxin extrusion (MATE) transporter by pyrimethamine increases the plasma concentration of metformin but does not increase antihyperglycaemic activity in humans. Diabetes Obes Metab. 2016 Jan;18(1):104-8. doi: 10.1111/dom.12577. Epub 2015 Oct 26. [PubMed:26381793]
  2. Kusuhara H, Ito S, Kumagai Y, Jiang M, Shiroshita T, Moriyama Y, Inoue K, Yuasa H, Sugiyama Y: Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects. Clin Pharmacol Ther. 2011 Jun;89(6):837-44. doi: 10.1038/clpt.2011.36. Epub 2011 May 4. [PubMed:21544077]
  3. May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [PubMed:27092232]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:38