美沙拉嗪肠溶片在健康人体的药代动力学及生物等效性研究

The pharmacokinetics and bioavailability of mesalamine enteric-coated tablets in healthy volunteers

目的:研究进口美沙拉嗪(5-ASA)肠溶片在健康人体的药代动力学,并与国产片剂进行生物等效性比较。方法:18名健康男性受试者分别随机交叉口服美沙拉嗪肠溶片试验药或参比药0.5 g,每8小时一次,连续七次。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,计算药代动力学参数并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)的药代动力学参数分别为:AUC0-t10.25±3.96和9.45±2.94μg.h.ml-1;Cmax2.21±1.49和1.98±1.18μg.ml-1;tmax4.83±2.32和4.47±3.15 h。其代谢产物(Ac-5-ASA)的药代动力学参数分别为:AUC0-t30.29±8.62和29.90±7.45μg.h.ml-1;Cmax3.21±1.02和3.28±1.20μg.ml-1;tmax5.94±2.54和4.31±3.29 h。经统计分析,上述各项参数间差别均无显著性意义(p>0.05)。进口美沙拉嗪肠溶片相对生物利用度为(108.4±27.4%)。结论:美沙拉嗪肠溶片试验药与参比药具有生物等效性。

Objective： To study the pharmacokinetics and relative bioavailability of mesalamine（5-ASA）and its active metabolite acetyl mesalamine （Ac-5-ASA）of imported mesalamine enteric-coated tablets in healthy male volunteers. Methods： Seven oral dose 0. 5g of tested mesalamine enteric-coated tablets and referenced mesalamine enteric-coated tablets were given to 18 healthy male volunteers in a randomized cross-over design. The plasma concentrations of unchanged 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 follows： AUC0-t were 10. 25±3.96 and 9.45±2. 94 μg·hμ ml^1 ;Cmax were 2. 21±1.49 and 1.98±1.18 μg · ml^-1 ;tmax,were 4.83±2. 32 and 4.47±3.15 h for test and reference mesalamine respectively. The main pharmacokinetic parameters of Ac-5-ASA were as follows： AUC0-t were 30. 29±8. 62 and 29. 90±7.45 μg · h · ml^-1 ,Cmax were 3. 21±1.02 and 3.28：kl. 20μg · ml^-1 ;tmax were 5.94±2. 54 and 4.31±3.29 h for test and reference mesalamine respectively. The relative bioavailability of test mesalamine enteric-coated tablets is （108.4 ±27.4%）%. Conlusions： The results of statistic analysis demonstrated that the two enteric-coated tablets are bioequivalent.