抗结核固定剂量复合剂的人体相对生物利用度研究

 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AUC_0→n，t_max，c_max，t_1/2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AUC_0→n为（77.92±14.36）μg·h·mL^-1，t_max为（1.71±0.88）h，c_max为（12.07±2.63）μg·mL^-1，t_1/2为（2.81±0.30）h；②参比药的药动学参数AUC_0→n为（75.37±19.33）μg·h·mL^-1，t_max为（2.13±0.93）h，c_max为（11.67±3.43）μg·mL^-1，t_1/2为（2.80±1.33）h；吡嗪酰胺：①受试药的药动学参数AUC_0→n为（416.24±77.00）μg·h·mL^-1，t_max为（1.12±0.50）h，c_max为（32.74±4.08）μg·mL^-1，t_1/2为（10.23±0.94）h；②参比药的药动学参数AUC_0→n为（420.39±63.79）μg·h·mL^-1，t_max为（1.27±0.59）h，c_max为（31.03±3.84）μg·mL^-1，t_0→n为（10.16±1.12）h；异烟肼：①受试药的药动学参数AUC_0→n为（21.17±13.48）μg·h·mL^-1，t_max为（1.06±0.42）h，c_max为（7.44±2.01）μg·mL^-1，t_1/2为（3.71±1.22）h；②参比药的药动学参数AUC_0→n为（19.85±13.76）μg·h·mL^{-1/sup>，t_max为（1.04±0.38）h，c_max为（6.89±2.44）μg·mL-1，t_1/2为（4.13±1.19）h。结论 国产与进口片为等效制剂，相对生物利用度分别为：利福平103.3%，吡嗪酰胺99.0%，异烟肼106.6%。}

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

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 RFP①The 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<\sub>（75.37±19.33）μg·h·mL^{-1<\sup>，tmax<\sub>（2.13±0.93）h，cmax（11.67±3.43）μg·mL-1，t1/2（2.80±1.33）h,respectively；The data of PZA①The pharmacokinetic parameters of domestic tablets were AUC0→n（416.24±77.00）μg·h·mL-1，tmax（1.12±0.50）h，cmax（32.74±4.08）μg·mL-1，t1/2（10.23±0.94）h,respectively；②The pharmacokinetic parameters of imported tablets were AUC0→n（420.39±63.79）μg·h·mL-1，tmax（1.27±0.59）h，cmax（31.03±3.84）μg·mL-1，t1/2（10.16±1.12）h,respectively.The data of INH①The pharmacokinetic parameters of domestic tablets were AUC0→n（21.17±13.48）μg·h·mL-1，tmax（1.06±0.42）h，cmax（7.44±2.01）μg·mL-1，t1/2（3.71±1.22）h,respectively;②The pharmacokinetic parameters of imported tablets were AUC0→n（19.85±13.76）μg·h·mL-1，tmax（1.04±0.38）h，cmax（6.89±2.44）μg·mL-1，t1/2（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.}}