酒石酸氢可酮片的人体药代动力学研究

摘要

目的：研究酒石酸氢可酮片的人体药代动力学。方法：本研究采用单次给药、平行设计试验方法，按照给药剂量5、10、15 mg（低、中、高）分为三组，每组10人。通过高效液相色谱串联质谱（HPLC-MS/MS）法测定血浆中氢可酮及其两种代谢产物（去甲基氢可酮和氢吗啡酮）的浓度。采用WinNonlin 6.1分析软件计算药代动力学参数。结果：氢可酮、去甲基氢可酮的线性范围均为0.05~50.00μg·L-1，氢吗啡酮的线性范围为0.01~10.00μg·L-1；受试者口服酒石酸氢可酮片后体内氢可酮、去甲基氢可酮的Cmax、AUC0-t和AUC0-∞随剂量增加而增加与给药剂量呈良好线性关系。研究过程中无严重不良事件发生。结论：HPLC-MS/MS测定法灵敏、准确、简便，适用于血浆中氢可酮及其代谢产物浓度的测定以及人体药代动力学研究。%Objective:To study the pharmacokinetics of hydrocodone tartrate tablets in human. Methods:We carried out single dose, parallel design study. Subjects were divided into three groups according to the dose of 5 mg, 10 mg, 15 mg (low, medium, high), and each group contained ten subjects. HPLC-MS/MS method was used for analysis of hydrocodone and its two metabolites (demethylation of hydrocodone and hydromorphone). WinNonlin 6.1 software was used to calculate the pharmacokinetic parameters. Results:Linearity was established in the range of 0.05–50.00μg·L-1 for hydrocodone and demethylation of hydrocodone, and 0.01–10.00μg·L-1 for hydromorphone. After the oral dose of hydrocodone tartrate tablets, Cmax, AUC0-t and AUC0-∞increased with the dose and showed a good linear relationship. There were no serious adverse events during the course of this study. Conclusion:HPLC-MS/MS is a sensitive and accurate method, which is suitable for the analysis of hydrocodone and its two metabolites (demethylation of hydrocodone and hydromorphone) in plasma and the pharmacokinetics study of hydrocodone tartrate tablets in human.