接受美沙酮维持治疗患者的细胞色素P450 2D6基因型与表型之间的不一致性。
A discordance between cytochrome P450 2D6 genotype and phenotype in patients undergoing methadone maintenance treatment.
作者信息
Shiran M R, Chowdry J, Rostami-Hodjegan A, Ellis S W, Lennard M S, Iqbal M Z, Lagundoye O, Seivewright N, Tucker G T
机构信息
Molecular Pharmacology and Pharmacogenetics, Division of Clinical Sciences (South), University of Sheffield, and Community Health Sheffield (CHS) Substance Misuse Services, Sheffield, UK.
出版信息
Br J Clin Pharmacol. 2003 Aug;56(2):220-4. doi: 10.1046/j.1365-2125.2003.01851.x.
AIMS
To assess CYP2D6 activity and genotype in a group of patients undergoing methadone maintenance treatment (MMT).
METHODS
Blood samples from 34 MMT patients were genotyped by a polymerase chain reaction-based method, and results were compared with CYP2D6 phenotype (n = 28), as measured by the molar metabolic ratio (MR) of dextromethorphan (DEX)/dextrorphan (DOR) in plasma.
RESULTS
Whereas 9% of patients (3/34) were poor metabolizers (PM) by genotype, 57% (16/28) were PM by phenotype (P < 0.005). Eight patients, who were genotypically extensive metabolizers (EM), were assigned as PM by their phenotype. The number of CYP2D6*4 alleles and sex were significant determinants of CYP2D6 activity in MMT patients, whereas other covariates (methadone dose, age, weight) did not contribute to variation in CYP2D6 activity.
CONCLUSIONS
There was a discordance between genotype and in vivo CYP2D6 activity in MMT patients. This finding is consistent with inhibition of CYP2D6 activity by methadone and may have implications for the safety and efficacy of other CYP2D6 substrates taken by MMT patients.
目的
评估一组接受美沙酮维持治疗（MMT）的患者的CYP2D6活性和基因型。
方法
采用基于聚合酶链反应的方法对34例MMT患者的血样进行基因分型，并将结果与通过血浆中右美沙芬（DEX）/右啡烷（DOR）的摩尔代谢率（MR）测定的CYP2D6表型（n = 28）进行比较。
结果
通过基因型检测，9%的患者（3/34）为慢代谢者（PM），而通过表型检测，57%（16/28）为PM（P < 0.005）。8例基因型为快代谢者（EM）的患者通过表型被判定为PM。CYP2D6*4等位基因数量和性别是MMT患者CYP2D6活性的重要决定因素，而其他协变量（美沙酮剂量、年龄、体重）对CYP2D6活性的变化没有影响。
结论
MMT患者的基因型与体内CYP2D6活性之间存在不一致。这一发现与美沙酮对CYP2D6活性的抑制作用一致，可能对MMT患者服用的其他CYP2D6底物的安全性和有效性产生影响。
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