溴吡斯的明新型复合物纳米乳在大鼠体内药代动力学及生物等效性研究

Pharmacokinetics and bioequivalence of pyridostigmine bromide novel phospholipids complex nanoemulsion in rats

摘要:

目的：研究溴吡斯的明（pyridostigmine bromide，ＰＢ）和水包油的溴吡斯的明新型复合物纳米乳（pyridostigmine bromide novel phospholipids complex nanoemulsion，PPCN）在大鼠体内的药代动力学，比较两者相对生物利用度和生物等效性。方法：本试验将12只大鼠随机分为2组，给药量相同，于预先设定不同的时间点采取血样，用HPLC法测定药物的血药浓度，DAS（2.1.1版）软件计算主要的药动学参数及生物等效性。结果：PB和水包油新型纳米乳PPCN的Cmax分别为1.49 mg/L和2.23 mg/L，AUC（0-72 h）分别为7.06 mg·h/L和14.12 mg·h/L。PB的Tmax为1.5 h，而PPCN的Tmax为4 h。PB的Cmax是PPCN的1.50倍，PPCN的AUC（0-72 h）是PB的2倍。经双单侧t检验，方差分析和非参数秩和检验AUC（0-72 h），Cmax和Tmax具有统计学差异（P分别为0.000，0.000，0.001）。结论：PPCN延长了PB在大鼠体内的作用时间，提高了PB在大鼠体内的口服生物利用度，PPCN与PB不具有生物等效性，且PPCN较PB更好。

Abstract:

Objective：To study the pharmacokinetics of pyridostigmine bromide and oil-in-water pyridostigmine bromide novel phos－pholipids complex nanoemulsion（PPCN） in rats，and to compare their relative bioavailability and bioequivalence. Methods：In this study，twelve rats were randomly divided into two groups and the same dose was administered. Blood samples was taken at different time points，and the plasma concentrations of the drugs were determined by HPLC. The DAS（2.1.1） software were used to calculate the main pharmacokinetic parameters and bioequivalence. Results：The Cmax of PB and PPCN were 1.49 mg/L and 2.23 mg/L，re－spectively. The AUC（0-72 h） of PB and PPCN were 7.06 mg·h/L and 14.12 mg·h/L respectively. The Tmax of PB was 1.5 h，and the Tmax of PPCN was 4 h. The Cmax of PPCN was 1.50 times that of PPCN，and the AUC（0-72 h） of PB was 2 times that of PPCN. The results of AUC（0-72 h） Cmax and Tmax were statistically different（P values were 0.000，0.000，0.001，respectively） by student’s t test，analysis of variance and wilconxon rank sum test. Conclusion：PPCN can not only prolong the action time of PB in rats，but also improve oral bioavailability of PB in rats，and PPCN and PB are not bioequivalent，and PPCN is better than PB.