title: Effects of cimetidine on the pharmacokinetics of proguanil in healthy subjects and in peptic ulcer patients.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Jos, Nigeria.
authors.forename: J A
authors.initials: JA
authors.lastname: Kolawole
authors.forename: A
authors.initials: A
authors.lastname: Mustapha
authors.forename: I
authors.initials: I
authors.lastname: Abdul-Aguye
authors.forename: N
authors.initials: N
authors.lastname: Ochekpe
authors.forename: R B
authors.initials: RB
authors.lastname: Taylor
mesh_terms: 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
chemical_list: D000897:Anti-Ulcer Agents; D000962:Antimalarials; D014227:Triazines; C026009:cycloguanil; D002927:Cimetidine; D002727:Proguanil