title: Pharmacokinetics of benflumetol given as a fixed combination artemether-benflumetol (CGP 56697) in Thai patients with uncomplicated falciparum malaria.
abstract: The pharmacokinetics of benflumetol as a fixed combination, artemether-benflumetol (CGP 56697), following three regimens [regimen A: four tablets at 0, 8, 24 and 48 h (320 mg artemether, 1,920 mg benflumetol); regimen B: two tablets at 0, 8, 24 and 48 h (160 mg artemether, 960 mg benflumetol); regimen C: four tablets at 0, 8 and 24 h (240 mg artemether, 1,440 mg benflumetol)] were investigated in 39 patients with acute uncomplicated falciparum malaria. All patients showed a rapid initial response with a median parasite clearance time of 40, 41 and 39.5 h and a fever clearance time of 27.8, 32 and 24.5 h for regimens A, B and C, respectively. In nine patients (two, four and three patients in regimens A, B and C, respectively), however, parasitemia reappeared in the peripheral blood smear between days 9 and 23. The pharmacokinetics of benflumetol were highly variable, with coefficients of variation in pharmacokinetic parameters ranging from 14.9% to 144%. Absorption and elimination of benflumetol were relatively slow. Median Cmax per dose (first dose) was significantly higher in regimen B (6.29 ng/ml/mg dose) than in regimen A (2.6 ng/ml/mg dose) and regimen C (3.06 ng/ml/mg dose). Mean T1/2z in regimen C (2.65 h) was significantly shorter than in regimen A (4.5 h) and regimen B (3.89 h). In patients on regimens A and B who showed a sensitive response, plasma concentrations of benflumetol were significantly higher than in those with treatment failure.
authors.affiliation: Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: K
authors.initials: K
authors.lastname: Na-Bangchang
authors.forename: J
authors.initials: J
authors.lastname: Karbwang
authors.forename: U
authors.initials: U
authors.lastname: Tasanor
authors.forename: A
authors.initials: A
authors.lastname: Thanavibul
authors.forename: E
authors.initials: E
authors.lastname: Farkad
authors.forename: R
authors.initials: R
authors.lastname: Mull
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D000077549:Artemether; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005449:Fluorenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D011897:Random Allocation; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000494:pharmacology*; D013785:Thailand; D013997:Time Factors
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D012717:Sesquiterpenes; D000077549:Artemether; D000078102:Lumefantrine