国产氨酚氢可酮片人体生物等效性研究

Bioequiavailability of domestic paracetamol and hydrocodone bitartrate tablets

目的:评价国产与进口氨酚氢可酮片的生物等效性。方法:采用双周期自身交叉试验设计,24名健康男性志愿者分别单剂量口服国产和进口氨酚氢可酮片1片,分别于给药前及给药后0.25、0.5、1、1.5、2、4、6、8、12、16、24 h采静脉血。采用高效液相色谱-质谱-质谱联用方法分别测定血浆中对乙酰氨基酚和重酒石酸氢可酮的浓度。结果:受试制剂与参比制剂中对乙酰氨基酚的tmax分别为(0.85±0.31)和(0.90±0.33)h,Cmax分别为(8.93±2.91)和(9.59±3.24)mg.L-1,t1/2分别为(3.19±0.71)和(3.20±1.48)h;AUC0-tn分别为(25.97±5.75)和(28.00±5.24)mg.L-1.h,AUC0-∞分别为(26.47±5.72)和(28.47±5.31)mg.L-1.h,受试制剂的相对生物利用度为(93.04±12.06)%。重酒石酸氢可酮的tmax分别为(1.04±0.78)和(0.96±0.751)h;Cmax分别为(22.93±6.45)和(21.49±6.19)μg.L-1;t1/2分别为(5.43±0.99)和(5.65±1.60)h;AUC0-tn分别为(128.59±32.75)和(116.84±29.98)μg.L-1.h;AUC0-∞分别为(135.43±34.05)和(124.74±32.37)μg.L-1.h;受试制剂的相对生物利用度为(112.77±26.54)%。结论:国产与进口氨酚氢可酮片具有生物等效性。

Objective： To evaluate the bioequiavailability of the domestic and the imported paracetamol and hydrocodone bitartrate tablets. Methods： The blood concentrations of paracetamol and hydrocodone bitartrate in 24 healthy male volunteers were determined by HPLC-MS-MS after a single oral dose with a randomized crossover method. Results： The main pharmacokinetic parameters of the paracetamol in the test and reference preparation were as follows： tmax were （0.85 ±0.31） and （0.90 ± 0.33） h, respectively; Cmax were （8.93 ± 2.91） and （9.59 ± 3.24） mg.L-1, respectively; tl/2 were （3.19± 0.71） and （3.20± 1.48） h, respectively; AUC0.t, were （25.97± 5.75） and （28.00 ± 5.24） mg.Ll.h, AUCo.0- ∞were （26.47 ± 5.72） and （28.47 ± 5.31） mg-Ll.h, respectively; the relative bioavailability of paracetamol in the test preparation was （93.04 ±12.06）%. The data of the hydrocodone bitartrate were as follows： tm~ were （1.04± 0.78） and （0.96 ± 0.751） h, respectively; Cmax were （22.93 ± 6.45） and （21.49 ±6.19） Ixg-L~, respectively; tl/2 were （5.43 ± 0.99） and （5.65 ±1.60） h, respectively; AUC0-∞ were （128.59 ±32.75） and （116.84 ± 29.98） pg.L-l＇h, respectively; AUC0-∞ were （135.43 ± 34.05） and （124.74 ± 32.37） μg.L-1.h, respectively; The relative bioavailability of the test preparation was （112.77 ± 26.54）%. Conclusion： The domestic paracetamol and hydrocodone bitartrate tablets are bioequivalent with imported oreDaration.