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.
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Received: 21 September 1995/Accepted in revised form: 15 January 1996
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Somogyi, A., Reinhard, H. & Bochner, F. Effects of omeprazole and cimetidine on the urinary metabolic ratio of proguanil in healthy volunteers. E J Clin Pharmacol 50, 417–419 (1996). https://doi.org/10.1007/s002280050133
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DOI: https://doi.org/10.1007/s002280050133