Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response.
Contribution of cytochrome P450 and ABCB1 genetic variability on methadone pharmacokinetics, dose requirements, and response.
复制标题
DOI：
10.1371/journal.pone.0019527
复制
发表时间：
2011-05-12
期刊：
影响因子：
3.7
通讯作者：
Torrens M
中科院分区：
文献类型：
--
作者：
Fonseca F;de la Torre R;Díaz L;Pastor A;Cuyàs E;Pizarro N;Khymenets O;Farré M;Torrens M
尽管美沙酮维持治疗(MMT)治疗阿片依赖障碍的疗效已被证实，但美沙酮的药代动力学对剂量要求和临床结果的影响仍存在争议。本研究的目的是分析美沙酮在有反应和无反应患者中的剂量，考虑可能有助于剂量充分性的药物遗传学和药代动力学因素。来自MMT社区项目的阿片依赖患者(符合精神疾病诊断和统计手册[第4版]标准)被招募。测定(R，S)-美沙酮、(R)-美沙酮、(S)-美沙酮的血药浓度，并研究其编码基因的等位基因变异。应答者和无应答者是通过随机尿检中检测到的非法阿片类药物消费来定义的。最终样本包括105名高加索血统的阿片依赖患者。有反应的患者接受了更高剂量的美沙酮，并接受了更长时间的治疗。两组间的基因频率没有差异。仅在结果状态、美沙酮剂量需求和血浆浓度方面发现了CYP2D6代谢表型的差异，超快速代谢剂的差异更大。在表型和应答者状态、美沙酮剂量要求以及美沙酮血药浓度之间没有发现其他差异。药代动力学因素可以解释MMT结果和美沙酮剂量需求的部分但不是全部差异。
Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements.
登录
查看更多内容
影响因子：
3.1
作者：
Crettol, Severine;Digon, Patricia;Eap, Chin B.
通讯作者：
Eap, Chin B.
影响因子：
2.9
作者：
Begré, S;von Bardeleben, U;Eap, CB
通讯作者：
Eap, CB
影响因子：
2.9
作者：
Elkader, Alexander K.;Brands, Bruna;Sproule, Beth Ann
通讯作者：
Sproule, Beth Ann
影响因子：
4.2
作者：
Epstein, David H.;Schmittner, John;Umbricht, Annie;Schroeder, Jennifer R.;Moolchan, Eric T.;Preston, Kenzie L.
通讯作者：
Preston, Kenzie L.
影响因子：
--
作者：
Bruijnzeel AW
通讯作者：
Bruijnzeel AW