pyrimethamine 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
2332 58-14-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • pyrimethamine
  • chloridin
  • chloridine
  • diaminopyritamin
  • pirimecidan
  • pirimetamin
  • pyrimethamin
One of the FOLIC ACID ANTAGONISTS that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis.
  • Molecular weight: 248.71
  • Formula: C12H13ClN4
  • CLOGP: 3
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 77.82
  • ALOGS: -3.14
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
75 mg O
75 mg O
75 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
S (Water solubility) 0.18 mg/mL Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine) 65 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 5.03 µM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 90 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.43 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.05 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.10 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 140 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.449 Moderate 0.76
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.698 Moderate 0.76
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 35.318 10^-6 cm/s Moderate 0.76
dh-clint Dog hepatocyte intrinsic clearance 2.148 uL/min/10^6 cells Moderate 0.76
dppb Dog plasma protein binding (% unbound) 10.620 % Moderate 0.76
fcs-ppb Fetal calf serum protein binding (% unbound) 25.880 % Moderate 0.76
herg hERG pIC50 5.303 pIC50 Moderate 0.76
hh-clint Human hepatocyte intrinsic clearance 0.908 uL/min/10^6 cells Moderate 0.76
hlm-clint Human liver microsomal intrinsic clearance 2.938 uL/min/mg protein Moderate 0.76
hppb Human plasma protein binding (% unbound) 7.330 % Moderate 0.76
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,CAMK2D,CDK5,CDK9,DYRK1B,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP3K21,MAPK7,PDK2,PIK3CA,PIK3CD,PIK3CG,PRKDC,SIK2 22
kinase-selectivity-class ACVR2A,ACVR2B 2
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 1.033 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 3.365 Moderate 0.76
mh-clint Mouse hepatocyte intrinsic clearance 7.079 Moderate 0.76
mppb Mouse plasma protein binding (% unbound) 10.750 Moderate 0.76
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 7.499 Moderate 0.76
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 16.630 % Moderate 0.76
rat-kpuu-brain Rat brain Kpuu 0.304 % High 1
rh-clint Rat hepatocyte intrinsic clearance 3.548 uL/min/10^6 cells Moderate 0.76
rh-fuinc Rat hepatocyte fraction unbound in incubation 59.500 % Moderate 0.76
rppb Rat plasma protein binding (% unbound) 7.610 % Moderate 0.76
solubility-dd Solubility at pH 7.4 in DMSO 231.739 uM Moderate 0.76

Approvals:

DateAgencyCompanyOrphan
Jan. 23, 1953 FDA AMEDRA PHARMS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pancytopenia 118.85 41.43 47 1047 120216 90507137
Cerebral toxoplasmosis 100.62 41.43 17 1077 1388 90625965
Drug reaction with eosinophilia and systemic symptoms 88.72 41.43 29 1065 42729 90584624
Bone marrow failure 71.46 41.43 23 1071 32198 90595155
Hepatocellular injury 49.51 41.43 17 1077 28941 90598412

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Urinary tract inflammation 59.35 32.08 10 1669 238 42619418
Pancytopenia 55.60 32.08 42 1637 117701 42501955
Enterocutaneous fistula 48.49 32.08 11 1668 1250 42618406
Conductive deafness 45.86 32.08 9 1670 508 42619148
Hepatitis cholestatic 44.01 32.08 16 1663 9808 42609848
Immune reconstitution inflammatory syndrome 39.85 32.08 15 1664 10128 42609528
Myopia 37.66 32.08 9 1670 1282 42618374
Pulmonary venous thrombosis 34.98 32.08 6 1673 159 42619497
Neutropenia 34.93 32.08 41 1638 199390 42420266
Cerebral toxoplasmosis 33.32 32.08 9 1670 2089 42617567

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pancytopenia 154.95 30.02 82 2508 209531 110377178
Cerebral toxoplasmosis 115.08 30.02 24 2566 3118 110583591
Drug reaction with eosinophilia and systemic symptoms 83.61 30.02 40 2550 82055 110504654
Bone marrow failure 80.38 30.02 35 2555 57813 110528896
Urinary tract inflammation 66.84 30.02 11 2579 387 110586322
Neutropenia 62.71 30.02 59 2531 374561 110212148
Hepatocellular injury 55.58 30.02 26 2564 50616 110536093
Conductive deafness 55.18 30.02 9 2581 299 110586410
Lymphopenia 51.56 30.02 23 2567 40147 110546562
Pathogen resistance 50.38 30.02 18 2572 17654 110569055
Immune reconstitution inflammatory syndrome 48.05 30.02 17 2573 16209 110570500
Enterocutaneous fistula 47.48 30.02 11 2579 2312 110584397
Mycobacterial infection 45.17 30.02 12 2578 4405 110582304
Cholestasis 43.98 30.02 24 2566 64494 110522215
Hepatitis cholestatic 39.40 30.02 15 2575 17551 110569158
Drug resistance 38.50 30.02 21 2569 56353 110530356
Myopia 37.25 30.02 9 2581 2262 110584447
Crystalluria 36.28 30.02 8 2582 1347 110585362
Toxic skin eruption 36.08 30.02 16 2574 27499 110559210
Pulmonary venous thrombosis 35.42 30.02 6 2584 252 110586457
Optic neuropathy 30.84 30.02 9 2581 4649 110582060

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC P01BD01 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Diaminopyrimidines
ATC P01BD51 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Diaminopyrimidines
ATC P01BF04 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Artemisinin and derivatives, combinations
ATC P01BF09 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Artemisinin and derivatives, combinations
FDA MoA N0000000191 Dihydrofolate Reductase Inhibitors
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000962 Antimalarials
MeSH PA D000977 Antiparasitic Agents
MeSH PA D000981 Antiprotozoal Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D005493 Folic Acid Antagonists
FDA EPC N0000175934 Dihydrofolate Reductase Inhibitor Antimalarial
CHEBI has role CHEBI:35442 antiparasitic agent
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35718 antifungal agent
CHEBI has role CHEBI:35820 antiprotozoal drug
CHEBI has role CHEBI:38068 antimalarial
CHEBI has role CHEBI:50683 EC 1.5.1.3 (dihydrofolate reductase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:75835 anti-anaemic agent

Related Drugs by ATC class:

P01BF Artemisinin and derivatives, combinations 11 drugs
amodiaquineartemetherartemisininartenimolartesunatelumefantrinemefloquinepiperaquinepyronaridinesulfadoxinesulfalene

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Malaria indication 61462000 DOID:12365
Toxoplasmosis indication 187192000 DOID:9965
Toxoplasmosis associated with acquired immunodeficiency syndrome indication 421666009
Chloroquine-Resistant Plasmodium Falciparum Malaria Prevention indication
Chloroquine Resistant Plasmodium Falciparum Malaria indication
Encephalitis due to Toxoplasmosis indication
Toxoplasmosis Prevention off-label use
Pneumocystis Carinii Pneumonia Prevention off-label use
Third trimester pregnancy contraindication 41587001
Acute nephropathy contraindication 58574008
Epilepsy contraindication 84757009 DOID:1826
Megaloblastic anemia due to folate deficiency contraindication 85649008 DOID:14026
Kidney disease contraindication 90708001 DOID:557
Anemia due to enzyme deficiency contraindication 111577008
Deficiency of glucose-6-phosphate dehydrogenase contraindication 124134002 DOID:2862
Folic acid deficiency contraindication 190633005
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Porphyria contraindication 418470004




🐶 Veterinary Drug Use

SpeciesUseRelation
Horses Myeloencephalitis (EPM) caused by Sarcocystis neurona Indication

🐶 Veterinary products

ProductApplicantIngredients
ReBalance Pegasus Laboratories Inc. 2

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 6.94 Basic
pKa2 0.6 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Dihydrofolate reductase Enzyme Ki 8.10 CHEMBL
Cytochrome P450 2C9 Enzyme Ki 4.29 WOMBAT-PK
Solute carrier family 22 member 1 Transporter IC50 4.87 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter INHIBITOR Ki 7.10 IUPHAR
Beta-hexosaminidase subunit alpha Enzyme IC50 5.51 CHEMBL
Beta-hexosaminidase subunit beta Enzyme IC50 5.35 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 8.72 PDSP
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme INHIBITOR Ki 9.72 CHEMBL CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme IC50 6.41 WOMBAT-PK
Dihydrofolate reductase Enzyme Ki 8.01 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.85 CHEMBL
Dihydrofolate reductase Enzyme Ki 8.92 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 6.60 WOMBAT-PK
Dihydrofolate reductase Enzyme IC50 5.30 CHEMBL
Dihydrofolate reductase Enzyme Ki 8.92 CHEMBL
Pteridine reductase 1 Enzyme IC50 4.87 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 7.01 WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 7.96 WOMBAT-PK
Solute carrier family 22 member 1 Transporter Ki 5.44 CHEMBL
Multidrug and toxin extrusion protein 1 Transporter Ki 6.84 CHEMBL
Dihydrofolate reductase Enzyme IC50 7 CHEMBL
Multidrug and toxin extrusion protein 2 Transporter INHIBITOR Ki 6.30 IUPHAR
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 9.07 CHEMBL

External reference:

IDSource
4017802 VUID
N0000146163 NUI
D00488 KEGG_DRUG
4017802 VANDF
C0034283 UMLSCUI
CHEBI:8673 CHEBI
CP6 PDB_CHEM_ID
CHEMBL36 ChEMBL_ID
DB00205 DRUGBANK_ID
D011739 MESH_DESCRIPTOR_UI
4993 PUBCHEM_CID
4800 IUPHAR_LIGAND_ID
2215 INN_ID
Z3614QOX8W UNII
9010 RXNORM
5396 MMSL
72370 MMSL
d00364 MMSL
002948 NDDF
373769001 SNOMEDCT_US
59589008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 0480-3720 TABLET 25 mg ORAL ANDA 18 sections
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 43598-672 TABLET 25 mg ORAL ANDA 24 sections
Pyrimethamine Human Prescription Drug Label 1 59651-590 TABLET 25 mg ORAL ANDA 22 sections
Daraprim HUMAN PRESCRIPTION DRUG LABEL 1 69413-330 TABLET 25 mg ORAL NDA 23 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-426 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-427 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-428 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-429 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-430 CAPSULE 12.50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70260-480 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-426 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-427 CAPSULE 25 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-428 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-429 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-430 CAPSULE 12.50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Leucovorin HUMAN PRESCRIPTION DRUG LABEL 2 70271-480 CAPSULE 50 mg ORAL unapproved drug other 1 sections
Pyrimethamine Human Prescription Drug Label 1 72603-262 TABLET 25 mg ORAL ANDA 22 sections
Pyrimethamine HUMAN PRESCRIPTION DRUG LABEL 1 72647-330 TABLET 25 mg ORAL NDA authorized generic 23 sections
Daraprim HUMAN PRESCRIPTION DRUG LABEL 1 83649-330 TABLET 25 mg ORAL NDA 23 sections