个性化的氢可酮疗法基于表型、遗传药理学和药代动力学定量。

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利纳雷斯OA, Fudin J,戴利,波士顿RC

个性化的氢可酮疗法基于表型、遗传药理学和药代动力学定量。

J痛苦。2015;12月31日(12):1026 - 35。doi: 10.1097 / AJP.0000000000000214。

PubMed ID

25621429 (在PubMed

]

文摘

目的:(1)量化氢可酮(HC)和hydromorphone (HM)代谢物药物动力学与药物基因学CYP2D6超高速代谢(嗯),广泛的代谢(EM),和穷人代谢(PM)代谢表型。(2)开发一个HC phenotype-specific剂量HC HM占生产战略使用临床药物动力学与患者安全药物基因学集成。设置:在硅片临床试验模拟。参与者:健康的白种男人和女人没有并发症或阿片类药物的历史,或任何其他药物或营养食品使用,26.3 + / - -5.7岁(意思是+ / -标准差;范围,19 - 36 y)和重量71.9 + / - -16.8公斤(范围、50到108公斤)。主要结果测量:CYP2D6 phenotype-specific HC临床药代动力学参数估计和phenotype-specific HM由HC的百分比。结果:经前综合症的下标HC性格与口头语和EMs相比。间隙降低了近60%,t1/2与EMs相比增加了68%。规范化为HC间隙是嗯> EM >点。HC主要由肝脏,消除由柯表示,在点减少了约70%。 However, HC's apparent Vd was not significantly different among UMs, EMs, and PM. The canonical order of predicted plasma HM concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean predicted HM levels were within HM's therapeutic range, which indicates HC has significant phenotype-dependent pro-drug effects. CONCLUSIONS: Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

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药物

氢可酮