卡维地洛人体药代动力学及生物利用度研究

Pharmacokinetics and bioavailability of carvedilol in healthy volunteers

目的测定卡维地洛 (carvedilol)志愿受试者体内的药代动力学 ,并与国外标准品地拉特润 (dilatrend)对照 ,评价其相对生物利用度。方法 10名健康男性志愿受试者 ,年龄 (39± 9)岁 ,随机交叉服用卡维地洛或地拉特润 40mg ,HPLC法测定给药后不同时间的血药浓度 ,并进行药代动力学参数计算和模型拟合。结果 10名受试者 6名符合一房室模型 ,另 4名符合二房室模型。卡维地洛的药代动力学主要参数 :一房室者达峰时间Tmax(1 7± 0 4)h、最大血药浓度Cmax(75± 32 )mg/L、曲线下面积AUC (314± 12 2 )mg/L·h、半衰期t1/2 (1 7± 0 8)h、清除速率CL (141± 43)L/h ;二房室者各值相应为 (1 0± 0 4)h、(113± 89)mg/L、(337± 85 )mg/L·h、(7 9± 5 6 )h、(111± 2 3)L/h。与地拉特润相比 ,两种制剂的药代动力学参数无显著差异(P >0 0 5 )。卡维地洛的相对生物利用度为 (98 9± 11 6 ) %。结论卡维地洛的药代动力学及生物利用度与国外标准品地拉特润近似 ,两种制剂生物等效。

Objective Compared with dilatrend, a proprietary preparation of carvedilol in Germany, the pharmacokinetics and bioavailability of domestic carvedilol was studied in 10 normal male healthy volunteers(age39±9) Methods A single dose of 40 mg carvedilol or dilatrend were given according to a randomized、crossover design The concentrations in plasma were determined by HPLC The pharmacokinetic parameters were calculated by computer Results Among the 10 volunteers, the concentration-time curve of carvedilol and dilatrend fitted to one-compartment model in 6 cases, two-compartment model in the other 4 cases, pharmacokinetics parameters of carvedilol in one-compartment model were: T max 1 7±0 4 h, C max 75±32 mg/L AUC314±122 mg/L(h, t 1/2 1 7±0 8 h, CL 141±43 L/h; the corresponding parameters in two-compartment model were: 1 0±0 4 h, 113±89 mg/L, 337±85 mg/L·h, 7 9±5 6 h, 111±23 L/h The parameters obtained from our studies showed no significant difference between the 2 preparations(P>0 05) The relative bioavailability of carvedilol to dilatrend was 98 9±11 6% Conclusion The pharmacokinetics and bioavailability of carvedilol are similar to those of dilatrend The 2 preparations are bioequvalent