甲硝唑结肠定位肠溶片在健康人体的药代动力学和生物等效性

Pharmacokinetics and bioequivalence of metronidazole colon-targeted tablet in healthy Chinese volunteers

目的评价甲硝唑结肠定位肠溶片(抗厌氧菌感染药)在健康人体的药代动力学和相对生物利用度。方法20名男性健康志愿者分别单剂、多剂交叉口服甲硝唑结肠定位肠溶片(受试制剂)和甲硝唑普通片(参比制剂)200mg,HPLC法测定甲硝唑浓度,DAS2.1软件计算主要药代动力学参数。结果主要药代动力学参数如下。单剂量:Cmax分别为(3.05±0.63),(4.44±0.56)μg·mL-1;tmax分别为(9.10±1.90),(1.50±0.60)h;t1/2分别为(9.93±2.14),(9.36±2.40)h;AUC0-48h分别为(48.74±11.56),(53.79±9.25)μg·h·mL-1;F为(91.30±18.60)%。多剂量:Cmax分别为(7.75±2.57),(10.27±2.08)μg·mL-1;Cmin(6.86±2.36),(6.34±1.48)μg·mL-1;Cav分别为(4.83±1.66),(7.65±1.59)μg·mL-1;DF分别为(0.31±1.26),(0.52±0.10);t1/2分别为(10.51±2.39),(9.97±2.40)h,AUCss分别为(38.65±13.30),(61.23±12.71)μg·h·mL-1,AUC0-48h分别为(158.23±66.84),(144.39±48.50)μg·h·mL-1,F为(110.10±25.20)%。结论2制剂吸收等效;但在胃肠道的吸收部位与速度不同;有良好的靶向结肠定位效果。

Objective To evaluate the pharmacokinetics and relative bioavailab in healthy mal refere volunteers ility of metronidazole colon - targeted tablets and normal tablet volunteers. Methods Metronidazole colon - targeted and nornce tablets 200 mg were given to twenty healthy male Chinese in a single and multiple oral dosing open labeled, randomized -way crossover study. Plasma metronidazole concentrations were determined by HPLC method. The main pharmacokinetic parameters were calculated with DAS 2. 1 software. Results The main pharmcokinetic parameters were as follows. Single dose ： Cmax were （ 3.05 ± 0.63 ） and （4.44 ±0.56） μg · mL^-1, tmax were （9.10 ±1.90） and （1.50 ±0.60） h, t1/2（9.93 ±2.14） and （9.36 ±2.40） h, AUC0-48h were （48.74 ± 11.56 ） and （53.79 ± 9.25 ） μg · h · mL^- 1, respectively, with F being （91.30 ± 18. 60）%. Multiple dose： Cmax Were （7. 75 ± 2. 57） and （10.27±2.08） μg · mL^-1, Cmax were （6.86 ±2.36） and （6.34 ± 1.48）μg · mL^-1, Cav were （4.83±1.66） and （7.65 ±1.59） μg · mL^-1, DF were （0.31 ± 1.26） and （0.52 ±0.10）, t1/2 were （10.51 ±2.39） and （9.97±2.40） h, AUCss（38.65 ±13.30） and （61.23 ±12.71） μg· h · mL^-1, AUC0-48h were （158.23 ± 66.84） and （ 144.39 ± 48.50） μg ·h · mL^ -1, respectively, with F being （ 110.10 ± 25.20） %. Conclusion The two praperations werebioequivalent in absorption with significant difference in the Cmax. While the time to peak of plasma concentration for the colon - targeted tablets was significantly delayed, which was a manifestation of its targeted release property in colon.