Effects of cimetidine on the pharmacokinetics of proguanil in healthy subjects and in peptic ulcer patients.
The pharmacokinetics of orally administered proguanil and its metabolites were determined in six healthy volunteers and in six peptic ulcer patients, before and after a 3-day course of cimetidine (400 mg given two times daily for 2 days and 400 mg on the third day 1 h before proguanil). Cimetidine significantly increased Cmax (P < 0.05), AUCo-alpha (P < 0.005) and elimination half-life t 1/2b of proquanil in plasma of healthy subjects. In ulcer patients, cimetidine significantly increased, AUCo-alpha (P < 0.05), elimination half life (P < 0.005) and Cmax. Cimetidine significantly reduced (P < 0.05) Total body clearance in both healthy subjects and in peptic ulcer patients. The Cmax and AUCo-alpha of the active metabolite cycloguanil was significantly decreased (P < 0.05) in both the healthy subjects and in the peptic ulcer patients. The Cmax of the inactive metabolite, 4-CPB was significantly decreased in healthy subjects and AUCo-alpha significantly decreased in peptic ulcer patients.
Kolawole
J A
JA
Department of Pharmaceutical Chemistry, University of Jos, Nigeria.
Mustapha
A
A
Abdul-Aguye
I
I
Ochekpe
N
N
Taylor
R B
RB
D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000962:Antimalarials / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D008297:Male; D010437:Peptic Ulcer / Q000188:drug therapy*; D002727:Proguanil / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D014227:Triazines / Q000493:pharmacokinetics
D000897:Anti-Ulcer Agents; D000962:Antimalarials; D014227:Triazines; C026009:cycloguanil; D002927:Cimetidine; D002727:Proguanil