Article date: May 2008
By: R. Michael Baldwin, Staffan Ohlsson, Rasmus Steen Pedersen, Jessica Mwinyi, Magnus Ingelman‐Sundberg, Erik Eliasson, Leif Bertilsson, in Volume 65, Issue 5, pages 767-774
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIMS
To investigate the influence of the CYP2C19*17 allele on the pharmacokinetics of omeprazole, a commonly used CYP2C19 probe drug, in healthy volunteers.
METHODS
In a single‐dose pharmacokinetic study, 17 healthy White volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1 received an oral dose of 40 mg of omeprazole. Plasma was sampled for up to 10 h postdose, followed by quantification of omeprazole, 5‐hydroxy omeprazole and omeprazole sulphone by high‐performance liquid chromatography.
RESULTS
The mean omeprazole AUC∞ of 1973 h nmol l−1 in CYP2C19*17/*17 subjects was 2.1‐fold lower [95% confidence interval (CI) 1.1, 3.3] than in CYP2C19*1/*1 subjects (4151 h nmol l−1, P = 0.04). A similar trend was observed for the sulphone metabolite with the CYP2C19*17/*17 group having a mean AUC∞ of 1083 h nmol l−1, 3.1‐fold lower (95% CI 1.2, 5.5) than the CYP2C19*1/*1 group (3343 h nmol l−1, P = 0.03). A pronounced correlation (r2 = 0.95, P < 0.0001) was seen in the intraindividual omeprazole AUC∞ and omeprazole sulphone AUC∞ values.
CONCLUSIONS
The pharmacokinetics of omeprazole and omeprazole sulphone differ significantly between homozygous CYP2C19*17 and CYP2C19*1 subjects. For clinically important drugs that are metabolized predominantly by CYP2C19, the CYP2C19*17 allele might be associated with subtherapeutic drug exposure.
DOI: 10.1111/j.1365-2125.2008.03104.x
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