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

Aims To further evaluate mephenytoin as a probe for CYP2C19 phenotyping. Methods Healthy subjects (n=2638) were phenotyped using the urinary (S)-mep henytoin to (R)-mephenytoin ratio. This method was evaluated for (a) the st ability 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 me tabolisers (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 metab olisers (PMs), the S/R-ratio increased after acid treatment. The intraindiv idual 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 i n 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 CYP2C1 9 phenotyping.