关键词: 双氯芬酸, 药物动力学, 单次和多次口服给药, 生物利用度

Abstract: Aim The comparative bioavailability of two diclofenac slow release tablets was studied after a single and repeated oral administration in 12 healthy male volunteers. Methods HPLC method with UV detection was used to determine the serum drug concentrations. Results The pharmacokinetic parameters obtained after single oral administration of the two formulations to the subjects in cross-over design showed that there was not significant difference between the two formulations in maximum concentration (C_max) and the area under the time-concentration curve (AUC) (P>0.05) whereas the time to reach the CC_max of the test tablets (TT) was shorter than that of the reference tablets (RT), with a significant difference between them. The relative bioavailability of TT was 98.11%. The result of the study on the repeated oral doses in 12 subjects indicated that there was no significant difference between the two tablets in C_max, C_min, C_ave, r and DF (P＞0.05). The duration of the minimum effective therapeutic drug level (T_mec) and the serum drug concentration peak-trough fluctuation of TT and RT in steady state were similar. Both TT and RT possessed good sustained release property. Conclution The two slow release tablets are bioequivalent formulation, with small difference between the two tablets in C_max and C_min. T_peak of TT in both single and repeated oral doses is significantly shorter than that of RT.

Key words: diclofenac, HPLC, pharmacokinetics, single and mutiple oral dose, bioavailability