Pharmacokinetics of chlorproguanil in man after a single oral dose of Lapudrine.
The pharmacokinetic parameters of chlorproguanil (Lapudrine) and its active metabolite, chlorcycloguanil, were determined in 6 healthy male volunteers after a single oral dose of 4 Lapudrine tables (80 mg). The mean maximum plasma chlorproguanil concentration was 36.7 +/- (SD) 7.9 ng/ml and was reached at 3.8 +/- 1.3 h. The chlorproguanil elimination half-life was 17.5 +/- 6.7 h and its plasma clearance was 1.28 +/- 0.12 l/h/kg. The mean whole blood to plasma ratio was 3.1 at 4 h after dosing. Chlorcycloguanil could not be quantified in plasma and whole blood at the detection limit of 10 ng/ml using a high-performance liquid chromatographic method. An excretion rate-time plot from urine data shows a rapid (t1/2 = 20 h) and a slow phase (t1/2 = 51 h) in the elimination of chlorcycloguanil. Our findings suggest that the current prophylactic regimen of chlorproguanil hydrochloride (20 mg weekly) may not be optimal in preventing infections with chloroquine-resistant falciparum malaria.
Veenendaal
J R
JR
Army Malaria Research Unit, Milpo, Ingleburn, Australia.
Edstein
M D
MD
Rieckmann
K H
KH
D000284:Administration, Oral; D000328:Adult; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D002727:Proguanil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D014227:Triazines
D014227:Triazines; C026009:cycloguanil; C007030:chlorproguanil; D002727:Proguanil