萘丁美酮分散片的人体药动学及生物等效性研究

 目的 建立测定萘丁关酮活性代谢物6-甲氧基-2-萘乙酸血浆浓度的HPLC紫外检测法,考察萘丁关酮在国人中的药动学及生物等效性。方法采用双周期交叉实验设计,选用20名健康志愿者单剂量po 1 000 mg萘丁关酮分散片或萘丁美酮片,用HPLC测定6-甲氧基-2-萘乙酸的血药浓度并计算药动学参数及相对生物利用度,进而对主要药动学参数进行统计分析。结果供试制剂与参比制剂的药时曲线均符合一级吸收的二房室开放模型,其主要药动学参数AUC_0-120分别为(884.2±288.1)与(90:3.6±368.7)mg·h·L^-1,AUC_0～∞分别为(924.2±299.4)与(945.4±384)mg·h·L^-1,c_max分别为(16.727±6.529)与(17.676±5.742)mg·L^-1,t_max分别为(8.3±7.2)与(7.9±7.3)h,t_1/2β分别为(24.8±5.5)与(24.7±6.2)h。供试制剂的相对生物利用度F为(100.8±22.5)％。两制剂InAUC_0～120,InAUC_0～∞和Inc_max方差分析、双单侧t检验的结果无显著性差异。结论 两国产萘丁关酮制剂具有生物等效性。

Study on the pharmacokinetics and bioequivalence of nabumetone in Chinese healthy volunteers

OBJECTIVE To develop a HPLC-UV method for the determination of 6-methoxy-2-naphthalene acetic acid (MNA),a active metabolite of nabumetone, in human plasma and study the pharmacokinetics profiles and bioequivalence of nabumetone dispersible tablet and nabumetone tablet in healthy Chinese volunteers.METHODS In a randomized two period crossover study, 20 healthy male volunteersreceived a single 1 000 mg dose of nabumetone dispersible tablet and nabumetone tablet. The plasmam concentrations of MNA were determinedby HPLC. The pharmacokinetic parameters of the two preparations and the relative bioavailability of dispersible tablet after oral administration were calculated and analyzed with statistical method. RESULTS The concentration-time curves of the two preparations were fitted to a two-compartment open model with first-order absorption. The main pharmacokinetic parameters of the two preparations were as follows:AUC_0～120(884.2±288.1) and (903.6±368.7)mg·h·L^-1, AUC_0～∞(924.2±299.4)and(945.4±384)mg·h·L^-1,c_max(16.727±6.529) and (17.676±5.742)mg·L^-1, t_max(8.3±7.2) and (7.9±7.3)h ,and t_1/2β(24.8±5.5) and (24.7±6.2)h, respectively. There were no significant difference between the two preparations. The relative bioavailability of the dispersible tablet was (97.9±13.6)% .CONCLUSION The results of the statistical analysis showed that the two preparations were bioequivalent.