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Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra‐individual reproducibility and occurrence of adverse events
Author(s) -
Tamminga Wim J.,
Wemer Johan,
Oosterhuis Berend,
Wieling Jaap,
Touw Daan J.,
De Zeeuw Rokus A.,
De Leij Lou F. M. H.,
Jonkman Jan H. G.
Publication year - 2001
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2001.01331.x
Subject(s) - mephenytoin , cyp2c19 , reproducibility , medicine , chemistry , chromatography , cytochrome p450 , metabolism
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.