Pharmacokinetic interactions of artemether and pyrimethamine in healthy male Thais.
The pharmacokinetics of a single oral dose of artemether (300 mg) and pyrimethamine (100 mg) given as each individual drug alone or as a drug combination (artemether 300 mg plus pyrimethamine 100 mg), were investigated in 8 healthy male Thai volunteers. Both artemether and pyrimethamine were rapidly absorbed after oral administration. Elimination of pyrimethamine was however, a relatively slow process compared with artemether, and thus resulted in a long terminal phase elimination half-life (50-106 hours). Pharmacokinetics of artemether and dihydroartemisinin following a single oral dose of artemether alone or in combination with pyrimethamine were similar. In contrast, coadministration of artemether resulted in significantly increased Cmax (medians of 818 vs 1,180 ng/ml) and contracted the apparent volume of distribution (medians of 3 vs 2.56 l/kg) of pyrimethamine.
Tan-ariya
P
P
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Na-Bangchang
K
K
Ubalee
R
R
Thanavibul
A
A
Thipawangkosol
P
P
Karbwang
J
J
D000328:Adult; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics*; D000077549:Artemether; D037621:Artemisinins; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D008297:Male; D011739:Pyrimethamine / Q000097:blood / Q000493:pharmacokinetics*; D012717:Sesquiterpenes / Q000097:blood / Q000493:pharmacokinetics*; D013785:Thailand
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077549:Artemether; D011739:Pyrimethamine