alexa Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra-individual reproducibility and occurrence of adverse events.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacogenomics & Pharmacoproteomics

Author(s): Tamminga WJ, Wemer J, Oosterhuis B, Wieling J, Touw DJ,

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Abstract AIMS: To further evaluate mephenytoin as a probe for CYP2C19 phenotyping. METHODS: Healthy subjects (n = 2638) were phenotyped using the urinary (S)-mephenytoin to (R)-mephenytoin ratio. This method was evaluated for (a) the stability of the S/R-ratio following sample storage, (b) the intraindividual reproducibility of the ratio, and (c) the occurrence of adverse events. RESULTS: After prolonged storage, the S/R-ratio of samples from extensive metabolisers (EM) increased up to 85\%. In 1.5\% of the cases (1 out 66), this led to incorrect classification of phenotype. In EMs, but not in poor metabolisers (PMs), the S/R-ratio increased after acid treatment. The intraindividual reproducibility of the mephenytoin phenotyping procedure was 28\%. No major side-effects were observed and there was no relationship between the incidence of side-effects and the phenotype of the subject. CONCLUSIONS: After prolonged storage the S/R-ratio significantly increased in EMs and, although low, the risk of incorrect classification should not be ignored. Our data support the use of mephenytoin as a safe drug for CYP2C19 phenotyping.
This article was published in Br J Clin Pharmacol and referenced in Journal of Pharmacogenomics & Pharmacoproteomics

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