Comparative Pharmacology
Head-to-head clinical analysis: DARAPRIM versus PROTOSTAT.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DARAPRIM versus PROTOSTAT.
DARAPRIM vs PROTOSTAT
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Daraprim (pyrimethamine) is a folic acid antagonist that inhibits dihydrofolate reductase (DHFR) in susceptible protozoa, thereby interfering with folate synthesis and blocking DNA synthesis and cell replication. It is synergistic with sulfonamides, which inhibit dihydropteroate synthase in the folate pathway.
Proto-oncogene tyrosine-protein kinase Src inhibitor; inhibits cell proliferation and induces apoptosis in cancer cells overexpressing Src.
50 mg orally once daily for 2 days, then 25 mg orally once daily for 4 weeks; for toxoplasmosis, a loading dose of 200 mg orally once daily for 1 day, followed by 50-75 mg orally once daily for 4-6 weeks, with folinic acid 10-25 mg daily.
250 mg orally three times daily after meals for 7-10 days; alternatively, 500 mg twice daily for 7 days.
None Documented
None Documented
Terminal elimination half-life is approximately 111 hours (range 54-148 hours) in adults. The long half-life allows weekly dosing for toxoplasmosis treatment.
8 hours (range 6-10 h); in renal impairment, half-life prolonged up to 20 hours; dose adjustment required for CrCl < 30 mL/min.
Primarily hepatic metabolism; renal excretion accounts for approximately 30% of elimination as unchanged drug and metabolites. Fecal excretion is minimal (<5%).
Renal: 70% as unchanged drug; biliary/fecal: 15% as metabolites; 15% other.
Category C
Category C
Antiprotozoal Agent
Antiprotozoal Agent