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|Title:||Effect of omeprazole and cimetidine on the urinary metabolic ratio of proguanil in volunteers.|
|Citation:||European Journal of Clinical Pharmacology, 1996; 50(5):417-419|
|Abstract:||OBJECTIVE:To examine the effects of omeprazole and cimetidine on the urinary recovery and metabolic ratio of proguanil in healthy subjects. METHODS:A metabolic interaction study was conducted in 12 young, healthy extensive metabolisers of proguanil, a CYP2C19 substrate, following a single 100 mg oral dose by analysis of urine collected for 8 hours. RESULTS:Concomitant administration of omeprazole (20 mg), a CYP2C19 substrate, had no significant effect on the urinary recovery of proguanil or cycloguanil, or the ratio of cycloguanil to proguanil [mean 0.76 (95% CI: 0.53 to 0.98) proguanil alone; mean 0.65 (95% CI: 0.40 to 0.89) proguanil plus omeprazole]. In contrast, cimetidine (400 mg), a general CYP inhibitor and renal organic cation secretion inhibitor, decreased the urinary recovery of cycloguanil and reduced the metabolic ratio from a mean of 0.76 to 0.54 (P < 0.01). In 3 poor metabolisers of proguanil, cimetidine had no effect on the proguanil metabolic ratio. CONCLUSION:The concomitant administration of omeprazole or cimetidine will not result in phenocopying extensive metabolisers of proguanil, although cimetidine inhibits the formation of cycloguanil in extensive metabolisers.|
|Keywords:||Humans; Cimetidine; Triazines; Omeprazole; Cytochrome P-450 Enzyme System; Aryl Hydrocarbon Hydroxylases; Mixed Function Oxygenases; Enzyme Inhibitors; Adult; Female; Male; Proguanil; Cytochrome P-450 CYP2C19|
|Appears in Collections:||Pharmacology publications|
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