美芬妥英作为CYP2C19表型分析的探针：样本储存的影响、个体内再现性及不良事件的发生情况
Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra-individual reproducibility and occurrence of adverse events.
作者信息
Tamminga W J, Wemer J, Oosterhuis B, Wieling J, Touw D J, de Zeeuw R A, de Leij L F, Jonkman J H
机构信息
Pharma Bio-Research Group BV, Science Park, NL-9471 GP Zuidlaren, University Center for Pharmacy, University of Groningen, The Netherlands.
出版信息
Br J Clin Pharmacol. 2001 May;51(5):471-4. 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.
目的
进一步评估美芬妥英作为CYP2C19表型分析探针的作用。
方法
采用尿中（S）-美芬妥英与（R）-美芬妥英的比值对2638名健康受试者进行表型分析。对该方法进行了以下评估：（a）样品储存后S/R比值的稳定性；（b）该比值的个体内重现性；（c）不良事件的发生情况。
结果
长期储存后，快代谢型（EM）受试者样品的S/R比值增加高达85%。在1.5%的病例中（66例中的1例），这导致了表型的错误分类。在EM中，而非慢代谢型（PM）中，酸处理后S/R比值升高。美芬妥英表型分析程序的个体内重现性为28%。未观察到严重副作用，且副作用发生率与受试者表型之间无关联。
结论
长期储存后，EM中S/R比值显著升高，尽管风险较低，但错误分类的风险不应被忽视。我们的数据支持将美芬妥英作为一种用于CYP2C19表型分析的安全药物。
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