美沙拉嗪栓剂在健康人体的药代动力学及生物等效性

Pharmacokinetics and bioequivalence of mesalamine suppository in healthy volunteers

目的 研究进口美沙拉嗪(5-ASA)栓剂的药代动力学过程及其生物等效性。方法 18名健康男性受试者用随机交叉给药方案,分别单次直肠给与美沙拉嗪栓剂试验药和参比药2 g,用柱前衍生化-HPLC-荧光法测定给药后不同时间点血浆中5-ASA和其活性代谢产物乙酰化-5-氨基水杨酸(Ac-5-ASA)的浓度,评价两种制剂的生物等效性。结果 试验药及参比药的原形药(5-ASA):AUC0-t分别为3.20±2.35和3.34±2.83 μg·h·mL-1;AUC0-8分别为3.22±2.37和3.38±2.89μg·h·mL-1;Cmax分别为0.48±0.16和0.42±0.17 μg·mL-1;tmax分别为4.61±2.8和5.72±3.30 h;t1/2分别为3.6 6±1.44和3.97±2.24 h。其代谢产物(Ac-5-ASA):AUC0-t分别为9.68±6.26和10.26±7.53μg·h·mL-1;AUC0-8分别为10.01±6.79和10.74±8.57 μg·h·mL-1;Cmax分别为1.23±0.41和1.10±0.37 μg·mL-1;tmax分别为5.00±2.20和6.1 1±3.48 h;t1/2分别为5.99±3.33和6.64±4.22 h。经统计学处理,上述各项参数间差别均无显著性意义(P>0.05)。美沙拉嗪栓剂相对生物利用度为(103.7±19.4)％。结论美沙拉嗪栓剂试验药与参比药具有生物等效性。

Objective To study the pharmacokinetics and bioequivalence of mesalamine (5-ASA) and its active metabolite acetyl mesalamine (Ac-5-ASA) of imported mesalamine suppository in healthy volunteers. Methods A single rectal dose 2 g of tested mesalazine suppository and referenced mesalmine suppository were given to 18 healthy volunteers in a randomized cross-over. The plasma concentrations of unaltered 5-ASA and its active metabolite Ac-5-ASA were determined by pre-column derivation HPLC method. The pharmacokinetic parameters and relative bioavailability were measured. Results The main pharmacokinetic parameters of 5-ASA were as follow: AUC0-1 were 3.20 ±2.35 and 3.34±2.83 μg·h·mL-1AUC0-8 were 3.22±37 and 3.38±2.83 μg·h·mL-1; Cmax were 0.48±0.16 and 0.42±0.17 μg-mL-1; tmax were 4.61±2.8 and 5.72±3.30 h; t1/2were3.66±1.44 and 3.97±2.24 h for test and reference masalamine, respectively. The main pharmacokinetic parameters of Ac-5-ASA were as follow: AUC0-1were 9.68± 6.26 and 10.26 ±7.53 μg·h·mL-1; AUC0-8 were 10.01±6.79 and 10.74±8.57 μg·h·mL-1;Cmaxwere 1.23±0.41 and 1.10 ±0.37 μg·mL-1;tmaxwere 5.00± 2.20 and 6.11 ±3.48 h; t1/2 were 5.99±3.33 and 6.64 ± 4.22 h for test and reference, respectively. The relative bioavailability of test mesalamine suppository was (103.7 ±19.4)%. Conlusions The results of statistics analysis demonstrated that two suppository were bioequivalent.