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Details

Stereochemistry ACHIRAL
Molecular Formula C23H16O6.C12H13ClN4
Molecular Weight 637.081
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PYRIMETHAMINE PAMOATE

SMILES

CCC1=C(C(N)=NC(N)=N1)C2=CC=C(Cl)C=C2.OC(=O)C3=C(O)C(CC4=C5C=CC=CC5=CC(C(O)=O)=C4O)=C6C=CC=CC6=C3

InChI

InChIKey=VJVWMYFEZGXNPC-UHFFFAOYSA-N
InChI=1S/C23H16O6.C12H13ClN4/c24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29;1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h1-10,24-25H,11H2,(H,26,27)(H,28,29);3-6H,2H2,1H3,(H4,14,15,16,17)

HIDE SMILES / InChI

Description

Pyrimethamine, sold under the trade name Daraprim, is one of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. In addition it was approved in Chemoprophylaxis of Malaria. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase 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. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

CNS Activity

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
1.5 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
DARAPRIM
Curative
DARAPRIM
Preventing
DARAPRIM

Cmax

ValueDoseCo-administeredAnalytePopulation
2.059 μg/mL
50 mg 1 times / day steady-state, oral
PYRIMETHAMINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
502.9 μg × h/mL
50 mg 1 times / day steady-state, oral
PYRIMETHAMINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
190.56 h
50 mg 1 times / day steady-state, oral
PYRIMETHAMINE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
13%
PYRIMETHAMINE plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
Toxoplasmosis: The adult starting dose is 50 to 75 mg of the drug daily, together with 1 to 4 g daily of a sulfonamide of the sulfapyrimidine type, e.g., sulfadoxine. This dosage is ordinarily continued for 1 to 3 weeks, depending on the response of the patient and tolerance to therapy. The dosage may then be reduced to about one half that previously given for each drug and continued for an additional 4 to 5 weeks. The pediatric dosage of DARAPRIM (PYRIMETHAMINE) is 1 mg/kg/day divided into 2 equal daily doses; after 2 to 4 days this dose may be reduced to one half and continued for approximately 1 month. The usual pediatric sulfonamide dosage is used in conjunction with DARAPRIM. Treatment of Acute Malaria: at a dosage of 25 mg daily for 2 days with a sulfonamide will initiate transmission control and suppression of non-falciparum malaria. The adult dosage for acute malaria is 50 mg for 2 days; children 4 through 10 years old may be given 25 mg daily for 2 days. In any event, clinical cure should be followed by the once-weekly regimen described below for chemoprophylaxis. Regimens which include suppression should be extended through any characteristic periods of early recrudescence and late relapse, i.e., for at least 10 weeks in each case. For Chemoprophylaxis of Malaria: Adults and pediatric patients over 10 years — 25 mg (1 tablet) once weekly. Children 4 through 10 years — 12.5 mg (1/2 tablet) once weekly. Infants and children under 4 years — 6.25 mg (1/4 tablet) once weekly.
Route of Administration: Oral
In Vitro Use Guide
Unknown