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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。
Objective To establish a LC-MS / MS method for the determination of metabolites of nicergoline dispersible tablets in human plasma and to study the pharmacokinetics and relative bioavailability of nicergoline dispersible tablets in healthy Chinese volunteers. Methods Twenty healthy volunteers were randomized to receive a single dose of nicergoline for 30 mg and reference preparations respectively. The metabolites of nicergoline in plasma samples were determined by LC-MS / MS at different time points. 10α-methoxy-9,10-dihydrolysericol (MDL). Data were processed using DAS 2.1 software to calculate pharmacokinetic parameters and relative bioavailability in both groups. Results The ρ max of MDL were (126.7 ± 44.6) and (128.0 ± 43.0) μg · L -1 after oral administration of nicergoline or the reference formulation respectively; t max was 3.3 ± (877.9 ± 267.0) and (862.6 ± 268.6)%, respectively; (1) the mean value of AUC_ (0 → t) was 1.7 ± 0.4 and 0.5 ± 0.4 h respectively; t 1/2 was 11.0 ± 7.6 and 10.1 ± 7.2 h, μg · h · L -1. The relative bioavailability of MDL in the test formulation was (106.0 ± 28.3)%. Conclusion The test preparation and the reference preparation are bioequivalent.