抗结核固定剂量复合剂的人体相对生物利用度研究

Relative bioavailability of fixed-dose combination of antituberculosis drugs in human

目的 研究抗结核固定剂量复合剂在健康人体内的相对生物利用度。方法 采用反相高效液相色谱法测定 12名健康志愿者口服国产和进口的抗结核固定剂量复合剂的血药浓度 ,计算两者药动学参数及相对生物利用度 ,并以AUC0→n,tmax,cmax,t1/ 2 为指标 ,用双单侧t检验分析国产片与进口片的生物等效性。结果 利福平 :①受试药的药动学参数AUC0→n为(77.92± 14.36 ) μg·h·mL-1,tmax为 (1.71± 0 .88)h ,cmax为 (12 .0 7± 2 .6 3) μg·mL-1,t1/ 2 为 (2 .81± 0 .30 )h ;②参比药的药动学参数AUC0→n为 (75 .37± 19.33) μg·h·mL-1,tmax为 (2 .13± 0 .93)h ,cmax为 (11.6 7± 3.43) μg·mL-1,t1/ 2 为 (2 .80± 1.33)h ;吡嗪酰胺 :①受试药的药动学参数AUC0→n为 (4 16 .2 4± 77.0 0 ) μg·h·mL-1,tmax为 (1.12± 0 .5 0 )h ,cmax为 (32 .74± 4.0 8) μg·mL-1,t1/ 2 为 (10 .2 3±0 .94)h ;②参比药的药动学参数AUC0→n为 (4 2 0 .39± 6 3.79) μg·h·mL-1,tmax为 (1.2 7± 0 .5 9)h ,cmax为 (31.0 3± 3.84) μg·mL-1,t1/ 2为 (10 .16± 1.12 )h ;异烟肼 :①受试药的药动学参数AUC0→n为 (2 1.17± 13.48) μg·h·mL-1,tmax为 (1.0 6± 0 .42 )h ,cmax为 (7.44±2 .0 1) μg·mL-1,t1/ 2 ?

OBJECTIVE To study the pharmacokinetics and the relative bioavailability of fixed-dose combination of antituberculosis drugs.METHODS A single oral dose of domestic and imported fixed-dose combination of antituberculosis drugs were given to 12-healthy volunteers in an open randomized cross-over way.The drug concentrations in serum were determined by HPLC method.The pharmacokinetic parameters as well as the relative bioavailability were measured.RESULTS The data of RFP:①The pharmacokinetic parameters of domestic tablets were AUC 0→n (77.92±14.36) μg·h·mL -1 , t max (1.71±0.88)h, c max (12.07±2.63)μg·mL -1 , t 1/2 (2.81±0.30)h,respectively;②The pharmacokinetic parameters of imported tablets were AUC 0→n (75.37±19.33)μg·h·mL -1 , t max (2.13±0.93)h, c max (11.67±3.43)μg·mL -1 , t 1/2 (2.80±1.33)h,respectively;The data of PZA:①The pharmacokinetic parameters of domestic tablets were AUC 0→n (416.24± 77.00 )μg·h·mL -1 , t max (1.12±0.50)h, c max (32.74±4.08)μg·mL -1 , t 1/2 (10.23±0.94)h,respectively;②The pharmacokinetic parameters of imported tablets were AUC 0→n (420.39±63.79)μg·h·mL -1 , t max (1.27±0.59)h, c max (31.03±3.84)μg·mL -1 , t 1/2 (10.16±1.12)h,respectively.The data of INH:①The pharmacokinetic parameters of domestic tablets were AUC 0→n (21.17±13.48)μg·h·mL -1 , t max (1.06±0.42)h, c max (7.44±2.01)μg·mL -1 , t 1/2 (3.71±1.22)h,respectively;②The pharmacokinetic parameters of imported tablets were AUC 0→n (19.85±13.76)μg·h·mL -1 , t max (1.04±0.38)h, c max (6.89±2.44)μg·mL -1 , t 1/2 (4.13±1.19)h,respectively.CONCLUSION The result of the statistical analysis showed that the two formations were bioequiverdent.The bioavailability of domestic tablet was RFP 103.3% ,PZA 99.0%,INH 106.6%,respectively.