异福酰胺片人体药代动力学及生物利用度研究

Pharmacokinetics and relative bioavailability of fixed-dose combination of antituberculous tablets——rifampin tablests in healthy volunteers

目的研究国产抗结核复方制剂异福酰胺片与进口异福酰胺片(Rifater卫肺特)比较的药代动力学及相对生物利用度。方法20名健康志愿者随机交叉单剂量口服两种复方制剂,采用RP-HPLC法,测定复方制剂中异烟肼、利福平、吡嗪酰胺血浆浓度。3P97程序计算主要药代动力学参数并对国产制剂作出生物等效评价。结果异烟肼、利福平、吡嗪酰胺在两种片刑的体内过程基本一致,测得国产与进口复方制剂中异烟肼C_(max)分别为(7.67±2.14)和(7.33±2.07)μg·L^(-1),T_(max)分别为(0.89±0.60)和(1.18±0.66)h,T_(1/2)分别为(3.13±1.07)和(3.39±0.77)h,AUC_(0-12)分别为(26.80±10.61)和(25.86±9.57)μg·L^(-1)。利福平C_(max)分别为(8.32±1.85)和(7.66±1.68),T_(max)分别为(2.52±1.47)和(2.65±1.42)h,T_(1/2)分别为(4.07±1.09)和(4.92±1.61)h,AUC_(0-24)分别为(60.77±17.62)和(59.02±17.65)μg·h·L^(-1)。吡嗪酰胺C_(max)分别为(24.96±4.69)和(23.93±3.27)μg·L^(-1),T_(max)分别为(1.35±O.73)和(1.78±1.12)h,T^(1/2)分别为(12.20±2.40)和(12.54±2.28)AUC_(0-36)分别为(334.50±60.21)和(341.63±58.97)μg·h·L^(-1)。国产复方片剂的异烟肼、利福平、吡嗪酰胺与进口复方片剂比较的相对生物利用度分别为(104.9±19.93)%、(105.82±27.03)%和(99.94±22.46)%。结论国产与进口两种复方片剂具有生物学等效性。

OBJECTIVE To study the pharmacokinetics and bioavailability of domestic fixed-dose combination of antituberculous tablets——rifampin tablets(isoniazid,rifampin plus pyrazinamide),using the imported Rifater tablets as control.METHOD Therandomized,cross-over study was conducted in 20 healthy volunteers.After a single close,the plasma drug levels were determined by RPHPLC and the pharmacokinetic parmalers were caculated.RESULTS The plasma concentration-time curves of the sample and the control almost showed no difference.The pharmacokinetic parameters of the sample and the control for isoniazid were as follows:C_(max) =(7.67 ±2.14)and(7.33±2.07)μg · L^(-1) T_(max) =(0.89 ±0.60)and(l.18 ±0.66) h,T_(l/2) =(3.13 ± 1.07) and(3.39 ±0.77) h,AL:C_(0-12) =(26.80 ± 10.61)and(25.86 ±9.57) μg · L^(-1),the pharmacokinetic paramaters for pyrazinamide wrere as follows;C_(max) =(24.96 ±4.69) and(23.93 ±3.27) μg · L^(-1),T_(max)=(1.35 ±0.73)and(1.78 ± 1.12)h,T_(1/2) =(12.20 ±2.40)and(12.54 ±2.28),AUC_(0-36) =(334.50 ±60.21)and(341.63 ±58.97) μg · L^(-1).The Relative bioavailability of domestic tablets was(104.9 ± 19.93) for ixoniazid,(105.82 ± 27.03)%for rifampin and(99.94 ± 22.46)%for isoniazid,(105.82 ±27.03)%for rifarnpind pyrazinamide.CONCLUSION The sample and the control tablets were bioequivalent.