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

• Published in: British journal of clinical pharmacology Vol. 51; no. 5; pp. 471 - 474
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-05-2001; Blackwell Science; Blackwell Science Inc
• Subjects: Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; CYP2C19; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System - classification; Cytochrome P-450 Enzyme System - metabolism; Drug Stability; Drug Storage; Female; General pharmacology; Humans; Male; Medical sciences; mephenytoin; Mephenytoin - metabolism; Mixed Function Oxygenases - classification; Mixed Function Oxygenases - metabolism; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Phenotype; phenotyping; Reproducibility of Results; Short Reports; Substrate Specificity; Human; Urine; Biological fluid; Pharmacogenetics; Healthy subject; Isozyme; Toxicity; Cytochrome P450; Chemical stability; Oral administration; Metabolism; Phenotype; Intraindividual comparison; Mephenytoin; Genetics; Pharmacokinetics; Polymorphism
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2001.01331.x

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.