Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra-individual reproducibility and occurrence of adverse events.
OBJECTIVE
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.
Tamminga
W J
WJ
Pharma Bio-Research Group BV, Science Park, NL-9471 GP Zuidlaren, University Center for Pharmacy, University of Groningen, The Netherlands.
Wemer
J
J
Oosterhuis
B
B
Wieling
J
J
Touw
D J
DJ
de Zeeuw
R A
RA
de Leij
L F
LF
Jonkman
J H
JH
D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000145:classification* / Q000378:metabolism; D004355:Drug Stability; D004356:Drug Storage; D005260:Female; D006801:Humans; D008297:Male; D008617:Mephenytoin / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000145:classification* / Q000378:metabolism; D010641:Phenotype; D015203:Reproducibility of Results; D013379:Substrate Specificity
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D008617:Mephenytoin