The mechanism of increased serum creatinine after administration of pyrimethamine and dapsone was evaluated for six healthy volunteers. Serum parameters, urine sediment, and clearances of creatinine, inulin, and para-aminohippurate were assessed prior to and 28 h after the ingestion of a single, combined dose of 100 mg of pyrimethamine and 200 mg of dapsone. In a second series, the same renal f...

In their recent article, de Kock et al. re-analyzed previously published data from a four-site African study (conducted in Mali, Mozambique, Sudan, and Zambia) that examined the pharmacokinetics of sulfadoxine-pyrimethamine in women during pregnancy and postpartum. Potential confounders not included in the original modeling reduced, but did not eliminate, between-site differences in pharmacokin...

The reduced binding of pyrimethamine to Ser108Asn (S108N) mutants of parasite dihydrofolate reductase (DHFR), which forms the basis of resistance of Plasmodium falciparum to pyrimethamine, is largely due to steric constraint imposed by the bulky side chain of N108 on Cl of the 5-p-Cl-phenyl group. This and other S108 mutants with bulky side chains all showed reduced binding to pyrimethamine and...

Chloroquine has been the mainstay of malaria chemotherapy for the past five decades, but resistance is now widespread. Pyrimethamine or proguanil form an important component of some alternate drug combinations being used for treatment of uncomplicated Plasmodium falciparum infections in areas of chloroquine resistance. Both pyrimethamine and proguanil are dihydrofolate reductase (DHFR) inhibito...

Each year, infections with the protozoan parasite Plasmodium falciparum kill 1 million people, mostly children in Africa. Intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) reduces the incidence of malaria and aims to prevent mortality in infants, children, and pregnant women. There is contradictory evidence as to whether this strategy may generate additional protection...

Objective: Two simple, accurate and reproducible spectrophotometric methods have been developed and validated for simultaneous estimation of pyrimethamine and sulphadoxine in combined dosage form. Methods: Pyrimethamine shows maximum absorbance at 285.6 nm and sulphadoxine shows maximum absorbance at 273.4 nm. In dual wavelength method, two wavelengths were selected for each drug in a way so th...

Proguanil and pyrimethamine are antifolate drugs with distinct chemical structures that are used commonly in the prophylaxis and treatment of Plasmodium falciparum malaria. Clinical reports and field studies have suggested that some parasites refractory to proguanil can be treated with pyrimethamine, and vice versa. Analysis of the P. falciparum dihydrofolate reductase (DHFR) from different par...

OBJECTIVE Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in...

Pyrimethamine (Daraprim (Burroughs Wellcome) ; 2,4diamino-5-p-chlorophenyl-6-ethylpyrimidine) is used in the treatment and prevention of malaria (1). When used in combination with one of the sulfonamides, it is also effective in the treatment of toxoplasmosis (2) and coccidiosis (3). Pyrimethamine is one of a series of 2,4-diaminopyrimidines which have been shown to be antagonists of folic acid...

Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections. Lowering transmission by reducing gametocyte infectivity would be an additional benefit. To examine the effect of such therapy on transmission, Gambian children with Plasmodium falciparum malaria were treated with standard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combinati...