人口管理后的氢可酮药代动力学分析氢可酮酒石酸氢盐延长释放胶囊。

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罗宾侬Melhem先生,厘米,Farr SJ,罗宾逊CY

人口管理后的氢可酮药代动力学分析氢可酮酒石酸氢盐延长释放胶囊。

Pharmacokinet。2013年10月,52(10):907 - 17所示。doi: 10.1007 / s40262 - 013 - 0081 - 6。

PubMed ID
23719682 (在PubMed
]
文摘

背景和目的:氢可酮是一种半合成的麻醉性镇痛药和止咳药。尽管氢可酮产品已经在市场上50多年来,相对很少有人知道其药物动力学。此外,没有发表的报道人口为氢可酮药代动力学分析。此外,当前标签hydrocodone-containing产品提供了一些指导的患者描述符氢可酮的药物动力学的影响。这个分析的目的是开发一个群体药代动力学的药物动力学模型,描述单个和多个后氢可酮口服剂量的氢可酮延长释放胶囊(氢可酮酒石酸氢盐ER胶囊)在健康受试者和病人,检查病人描述符对药代动力学参数的影响和评估的dose-proportionality氢可酮药代动力学。方法:总共有4714等离子体氢可酮浓度从220受试者可供分析。七个研究的数据提取(五阶段1和阶段2的两个研究)。两舱制开放乳头状模型与线性消除和复杂的吸收模型被用来适应数据,使用NONMEM 7.1.2 ((R))版本的软件。吸收模型涉及两个序列一阶吸收过程的延迟在第一个过程中通过多种交通方式隔间。协变量分析使用标准向前选择跟着向后消除过程。 Model evaluation was performed using a prediction-corrected visual predictive check (pcVPC). RESULTS: The population estimates of apparent oral central volume of distribution and apparent oral linear clearance were 714 L and 64.4 L/h, respectively. The first absorption process was rapid. Creatinine clearance and body surface area (BSA) were statistically significant predictors of the apparent oral clearance and apparent oral volume of distribution. The pcVPC indicated that the model provided a robust and unbiased fit to the data. CONCLUSIONS: A linear model for hydrocodone elimination provided an adequate fit to the observed data over the entire dose range, which supports that hydrocodone bitartrate ER capsules exhibit dose-proportional pharmacokinetics. The formulation of hydrocodone bitartrate ER capsules results in absorption profiles that are variable across and within subjects. Despite the variability in absorption profiles, a relatively simple model provided an adequate fit to the data. Creatinine clearance and BSA were statistically significant predictors of the apparent oral clearance and apparent oral volume of distribution. Absorption characteristics of hydrocodone bitartrate ER capsules should still allow effective plasma concentrations of hydrocodone to be reached quickly and for effective concentrations to be maintained for a long period.

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