CYP2D6*10等位基因对托培里松药动学的影响

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Chang‑Keun Cho, Ji-Young Byeon, Pureum Kang, Jung-In Park, Choon-Gon Jang, Seok-Yong Lee, Chang-Ik Choi, Jung‑Woo Bae, Yun Jeong Lee
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引用次数: 3

摘要

托培力松,一种用于中风后痉挛的肌肉松弛剂,据报道具有非常广泛的个体间药代动力学变异性。它主要由CYP2D6代谢,其次由CYP2C19和CYP1A2代谢。CYP2D6是一种高度多态性酶,CYP2D6*wt/*wt、CYP2D6*wt/*10和CYP2D6*10/*10基因型占韩国人群CYP2D6基因型的90%以上。因此,本研究探讨了CYP2D6*10对托培里森酮药代动力学的影响,以阐明个体间差异较大的原因。采用液相色谱-串联质谱法(LC-MS /MS)测定64名健康韩国人口服tolperisone 150 mg的血浆tolperisone浓度。CYP2D6*10/*10和CYP2D6*wt/*10组Cmax显著高于CYP2D6*wt/*wt组,CL/F显著低于CYP2D6*wt/*wt组。CYP2D6*10/*10组和CYP2D6*wt/*10组的AUCinf分别比CYP2D6*wt/*wt组高5.18倍和2.25倍。各基因型组的Cmax和AUC值存在较大差异,且随着CYP2D6活性的降低,差异更大。上述结果提示,CYP2D6基因多态性显著影响托培里松的药代动力学,CYP2D6以外的其他因子也可能对托培里松的药代动力学有显著影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone

Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone

Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and CYP2D6*wt/*wt, CYP2D6*wt/*10 and CYP2D6*10/*10 genotypes constitute more than 90% of the CYP2D6 genotypes in the Korean population. Thus, effects of the CYP2D6*10 on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The CYP2D6*10/*10 and CYP2D6*wt/*10 groups had significantly higher Cmax and lower CL/F values than the CYP2D6*wt/*wt group. The AUCinf of CYP2D6*10/*10 and CYP2D6*wt/*10 groups were 5.18-fold and 2.25-fold higher than the CYP2D6*wt/*wt group, respectively. There were considerable variations in the Cmax and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of CYP2D6 significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.

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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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