Steady-state kinetics of proguanil and its active metabolite, cycloguanil, in man.
The pharmacokinetics of proguanil and its active metabolite, cycloguanil, were determined at steady-state in 6 healthy male volunteers after daily administration of 2 Paludrine tablets (200 mg proguanil hydrochloride). A maximum plasma proguanil concentration of 130.3 +/- 16.0 ng/ml (mean +/- SD) was reached at 3.8 +/- 1.3 h while a maximum cycloguanil concentration of 52.0 +/- 15.2 ng/ml was obtained at 5.3 +/- 1.0 h after dosing. The elimination half-lives of proguanil and cycloguanil were 14.5 +/- 3.0 h and 11.7 +/- 3.1 h, respectively. The plasma clearance of proguanil was 1.43 +/- 0.33 l/h/kg and the apparent volume of distribution was 30.7 +/- 12.3 l/kg. Renal clearance of proguanil (0.33 +/- 0.19 l/h/kg) was about 23% of the plasma clearance and 35.6 +/- 9.6% of the oral dose was recovered as proguanil and cycloguanil.
Edstein
M D
MD
Army Malaria Research Unit, Milpo, Ingleburn, Australia.
Veenendaal
J R
JR
Scott
H V
HV
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 / Q000378:metabolism / Q000493:pharmacokinetics*; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics*
D014227:Triazines; C026009:cycloguanil; D002727:Proguanil