NONMEM法评价盐酸氨溴索片的生物等效性

Evaluation of bioequivalancy of ambroxol hydrochloride tablets by NONMEM approach

目的 用NONMEM法估算盐酸氨溴索 (AMB)片剂的药代动力学参数 ,并分析相对生物利用度和生物等效性。方法 HPLC法测定 2 0名男性健康受试者随机化设计两周期自身交叉对照试验服用 60mg进口、国产AMB的片剂后的血药浓度 ,用NONMEM软件一步法估算AMB口服线性二房室开放模型的药代动力学参数和相对生物利用度 ,评价其生物等效性 ,并与 3P97程序法分析结果比较。结果 用NONMEM法估算片剂的生物利用度为 (95 9± 0 0 2 ) % ,90 %可信区间为 94 7%～ 97 1 % ,与 3P97法一致。片剂的参比制剂与试验制剂的药代动力学参数 :Ka分别为2 0 3± 1 50h- 1 和 2 48± 1 37h- 1 ,α分别为 0 30 2± 0 0 390h- 1 和 0 2 81± 0 0 4 4 6h- 1 ,β分别为 0 0 72 6± 0 0 0 2 38h- 1 和 0 0 694± 0 0 0 0 31h- 1 ,Vd 分别为 2 61± 53 9L和 2 58± 46 2L ;与 3P97结果比较均无显著性差异 (P >0 0 5)。结论 :NONMEM法可为生物利用度及生物等效性分析提供简便快捷的辅助方法。

Objective To evaluate the pharmacokinetics, relative bioavailability and bioequivalancy of ambroxol hydrochloride (AMB) tablets by NONMEM approach. Methods Plasma concentrations were determined by HPLC in 20 healthy male volunteers after a single oral dose of reference and test drugs as randomized two periods self controlled crossover design. NONMEM program was applied to estimating the pharmacokinetics and relative bioavailability of AMB. The relationship of results between NONMEM and 3P97 method was evaluated by t test. Results The relative bioavailability of AMB tablets was (95.9±0.02)%. The 90% confidence interval was 94.7%～97.1%. The pharmacokinetic parameters of reference and test tablet as follows: Ka were 2.03±1.50h -1 and 2.48±1.37h -1 , α were 0.302±0.0390h -1 and 0.281±0.0446h -1 , β were 0.0726±0.00238h -1 and 0.0694±0.00031h -1 , Vd were 261±53.9L and 258±46.2L, respectively. The result of t test displayed that there no significant differences ( P> 0.05) between NONMEM and 3P97 method. Conclusions NONMEM approach could be used as adjuncts to the current methods for the bioavailability and bioequivalancy assessment.