Effects of omeprazole and cimetidine on the urinary metabolic ratio of proguanil in healthy volunteers.
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.


CONCLUSIONS
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.
Somogyi
A A
AA
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
Reinhard
H A
HA
Bochner
F
F
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D002927:Cimetidine / Q000494:pharmacology*; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000652:urine; D009853:Omeprazole / Q000494:pharmacology*; D002727:Proguanil / Q000652:urine*; D014227:Triazines / Q000652:urine
D004791:Enzyme Inhibitors; D014227:Triazines; C026009:cycloguanil; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D002727:Proguanil