尼麦角林分散片在人体的生物等效性

Bioequivalence of nicergoline dispersible tablets in healthy volunteers

目的建立人血浆中尼麦角林分散片代谢产物的LC-MS/MS测定方法,并研究尼麦角林分散片在健康中国志愿者体内的药动学及相对生物利用度。方法 20名男性健康志愿者采用双周期随机交叉给药方案,分别单剂量口服30mg的尼麦角林试验制剂与参比制剂,采用LC-MS/MS法测定不同时刻血浆样本中尼麦角林代谢产物10α-甲氧基-9,10-二氢麦角醇(MDL)的浓度。应用DAS 2.1软件处理数据,计算2组的药动学参数及相对生物利用度。结果口服尼麦角林试验制剂或参比制剂后,MDL的ρ_(max)分别为(126.7±44.6)和(128.0±43.0)μg·L^(-1);t_(max)分别为(3.3±1.7)和(2.4±0.5)h;t_(1/2)分别为(11.0±7.6)和(10.1±7.2)h;AUC_(0→t)分别为(877.9±267.0)和(862.6±268.6)μg·h·L^(-1)。试验制剂中MDL的相对生物利用度为(106.0±28.3)%。结论试验制剂与参比制剂具有生物等效性。

AIM To determine nicergoline dispersible tablets in human plasma by LC-MS/MS and to evaluate the pharmacokinetics and relative bioavailability of nicergoline dispersible tablets in healthy volunteers.METHODS A single oral dose of 30 mg nicergoline dispersible tablets,test drug or reference drug,was given to 20 healthy male volunteers according to an open randomized crossover study.The plasma concentration of 10α-methoxy-9,10-dihydroergotamine alcohol （MDL）,the active metabolite nicergoline,was determined by LC-MS/MS in different times.The data of pharmacokinetic parameters and relative bioavailability were processed by DAS 2.1 software.RESULTS The main pharmacokinetic parameters of MDL in test preparation and reference preparation were obtained as follows：ρ_（max） was（126.7±44.6） and （128.0±43.0）μg·L^（-1）;t_（max） was（3.3±1.7） and（2.4±0.5）h;t_（1/2） was（11.0±7.6） and（10.1±7.2） h; AUC_（0→t） was（877.9±267.0） and（862.6±268.6）μg·h·L^（-1）,respectively.The average relative bioequivalence of test preparation MDL was（106.0±28.3）%.CONCLUSION The results of statistical analysis show that two preparations are bioequivalent.