CYP2C19多态性对奈非那韦的影响在艾滋病患者M8生物转化。

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雷赫特D, Mentre F, Tran E, Auleley年代,鲑鱼D, Duval X Treluyer JM

CYP2C19多态性对奈非那韦的影响在艾滋病患者M8生物转化。

Br中国新药杂志。2008年4月,65 (4):548 - 57。doi: 10.1111 / j.1365-2125.2007.03039.x。Epub 2007年10月8日。

PubMed ID

17922881 (在PubMed

]

文摘

这个话题已经知道是什么:*奈非那韦是一种HIV蛋白酶抑制剂,通过CYP2C19运输车22的底物和代谢,CYP3A4和CYP3A5酶。*药代动力学研究显示广泛的个人间的变异性奈非那韦的浓度,其中一些变化可能引起的药物代谢或转运体基因变体。对CYP3A4 * * 1 b和CYP3A5 * 3多态性,三项协议,结果显示没有区别这些不同基因型患者之间在奈非那韦的浓度。*不过,凋亡和CYP2C19多态性有矛盾的研究,显示浓度不影响奈非那韦的浓度或修改可能影响病毒学应答。这个研究补充道:*一个患者* 1 / * 2 * 2 * 2为CYP2C19基因型有奈非那韦M8生物转化相比,除以2 * 1 / * 1例。*没有证据表明任何影响凋亡多态性奈非那韦吸收能被检测出来。目的:评价CYP2C19多态性的影响在奈非那韦和M8药代动力学变化在人类免疫缺陷病毒感染患者和研究药代动力学接触之间的联系和短期疗效和毒性。方法:奈非那韦(n = 120)和M8 (n = 119)浓度测定在34个蛋白酶inhibitor-naive病人。两周后开始治疗,血液采集标本,1、3和6 h后药物管理局。CYP3A4基因分型,3 a5, 2 c19和凋亡。 A population pharmacokinetic model was developed to describe nelfinavir-M8 concentration time-courses and to estimate interpatient variability. The influence of individual characteristics and genotypes were tested using a likelihood ratio test. Estimated mean (C(mean)), maximal (C(max)) and trough (C(trough)) nelfinavir and M8 concentrations were correlated to short-term virological efficacy and tolerance using Spearman nonparametric correlation tests. RESULTS: A one-compartment model with first-order absorption, elimination and metabolism to M8 best described nelfinavir data. M8 was modelled by an additional compartment. Mean pharmacokinetic estimates and the corresponding intersubject variabilities were: absorption rate 0.17 h(-1) (99%), absorption lag time 0.82 h, apparent nelfinavir total clearance 52 l h(-1) (49%), apparent nelfinavir volume of distribution 191 l, M8 elimination rate constant 1.76 h(-1) and nelfinavir to M8 0.39 h(-1) (59%) in *1/*1 patients and 0.20 h(-1) in *1/*2 or *2/*2 patients for CYP2C19*2. Nelfinavir C(mean) was positively correlated to glycaemia and triglyceride increases (P = 0.02 and P = 0.04, respectively). CONCLUSIONS: The rate of metabolism of nelfinavir to M8 was reduced by 50% in patients with *1/*2 or *2/*2 genotype for CYP2C19 compared with those with *1/*1 genotype.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
奈非那韦	细胞色素P450 3 a5	蛋白质	人类	没有	底物 抑制剂	细节