ISSN:
1432-1041
Keywords:
Key words Proguanil
;
Omeprazole
;
Cimetidine; druginteraction
;
metabolic ratio
;
CYP2C19
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050133
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