氨酚氢可酮片的生物等效性研究

目的:评价两种氨酚氢可酮片的生物等效性。方法:以市售氨酚氢可酮片为参比制剂,以自制氨酚氢可酮片为受试制剂,采用双制剂双周期交叉试验设计,在健康男性(n=20)体内进行药动学研究,清洗期为1周。分别于每一周期给药前和给药后各时间点取肘静脉血,分离血浆。分别采用高效液相色谱(HPLC)法测定对乙酰氨基酚、液质联用(LC-MS/MS)法测定氢可酮的血药浓度,计算两者的药动学参数和相对生物利用度,评价受试制剂与参比制剂的生物等效性。结果:受试制剂和参比制剂中对乙酰氨基酚的主要药动学参数t1/2分别为(3.900±1.926)、(4.088±1.731)h,tmax分别为(0.775±0.197)、(0.763±0.190)h,cmax分别为(15.932±3.695)、(16.952±3.939)μg/ml,AUC0-24 h分别为(64.270±26.625)、(64.723±26.297)μg·h/ml,AUC0-∞分别为(67.716±33.219)、(67.661±33.150)μg·h/ml;受试制剂中对乙酰氨基酚的相对生物利用度为(100.9±14.5)%。受试制剂和参比制剂中氢可酮的主要药动学参数t1/2分别为(5.377±0.862)、(5.318±1.382)h,tmax分别为(1.438±0.590)、(1.513±0.604)h,cmax分别为(21.722±6.102)、(20.572±5.380)ng/ml,AUC0-24 h分别为(135.493±33.835)、(133.009±30.810)μg·h/ml,AUC0-∞分别为(142.386±35.767)、(139.243±31.540)μg·h/ml;受试制剂中氢可酮相对生物利用度为(102.9±16.9)%。结论:两种氨酚氢可酮片生物等效。

Bioequivalence Study of Paracetamol and Hydrocodone Bitartrate Tablets

OBJECTIVE：To evaluate the bioequivalence of two kinds of Paracetamol and hydrocodone bitartrate tablets.METHODS：Pharmacokinetic experiments on healthy male volunteers （n =20） were performed by double-agent double-cycle crossover trial with self-made Paracetamol and hydrocodone bitartrate tablet as test preparation and the commercial ones as reference preparation with cleaning period of one week.Blood samples were taken from ulnar vein at different time points （before and after administration of drugs） for separation of plasma.The concentration of paracetamol was determined by HPLC and that of hydrocodone by LC-MS/MS.The pharmacokinetic parameters and relative bioavailability of the two preparations were computed and the bioequivalence of the two agents were evaluated.RESULTS：The main pharmacokinetic parameters of paracetamol in test preparation vs.reference preparation were as following：t12 was （3.900±1.926）h vs.（3.088±1.731）h; tmax was （0.775±0.197）h vs.（0.763± 0.190）h; cmax was （15.932±3.695）μg/ml vs.（16.952±3.939）mg/ml; AUC0-24h was （64.270±26.625）μg·h/ml vs.（64.72 3±26.297） μg· h/ml; AUC0-∞ was （67.716± 33.219） μg· h/ml vs.（67.661 ± 33.150） μg· h/ml; the relative bioavailability of paracetamol in the test agent was （100.9±14.5）％.The main pharmacokinetics parameters of hydrocodone in test preparation vs.reference preparation were as following：t1/2 was （5.377±0.862）h vs.（5.318±1.382）h; tmax was （1.438±0.590）h vs.（1.513±0.604）h; cmax was （21.722±6.102） ng/ml vs.（20.572±5.380）ng/ml; AUC0-24 h was （135.493±33.835） μg· h/ml vs.（133.009±30.810） μg· h/ml; AUC0-∞ was （142.386± 35.767） μg· h/ml vs.（139.243 ± 31.540） μ g· h/ml; the relative bioavailability of hydrocodone in the test preparation was （102.9 ± 16.9） ％.CONCLUSIONS：Two kinds of paracetamol and hydrocodone bitartrate tablets are bioequivalent.