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

Article date: May 2001

By: Wim J. Tamminga, Johan Wemer, Berend Oosterhuis, Jaap Wieling, Daan J. Touw, Rokus A. De Zeeuw, Lou F. M. H. De Leij, Jan H. G. Jonkman, in Volume 51, Issue 5, pages 471-474

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.

DOI: 10.1046/j.1365-2125.2001.01331.x

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