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本研究进行了盐酸特拉唑嗪口服渗透泵控释片在健康人体内的药物动力学分析。运用随机交叉实验设计,20名健康受试者单剂量、多剂量口服受试制剂、参比制剂,采用HPLC法测定血浆中盐酸特拉唑嗪的浓度,使用3P97软件计算药物动力学参数。单剂量口服控释片、普通片各4 mg后,普通片的C_(max)(120.56±23.15)ng/mL明显高于控释片的C_(max)(95.27±16.35)ng/mL。控释片口服给药后的T_(max)为(2.65±0.82)h,较普通片T_(max)(1.27±0.61)h延迟,有显著性差异(P<0.05),其相对生物利用度为(105.85±6.12)%。受试者多剂量口服普通片与控释片后药物动力学参数稳态时曲线下面积(AUC_(ss))分别为(1275.17±175.35)、(1382.65±205.31)ng·h/mL;C_(max)分别为(128.15±22.37)、(98.57±18.16)ng/mL;T_(max)分别为(1.35±0.71)、(2.76±0.85)h;平均稳态血药浓度(C_(av))分别为(53.13±9.12)、(57.61±9.25)ng/mL;血药浓度波动度(DF)分别为(2.25±0.26)%和(1.62±0.25)%,其相对生物利用度为(108.43±6.26)%。经统计学检验表明,这两种制剂的AUC_(0-48 h)、AUC_(0-∞)具有生物等效性,普通片与控释片口服时吸收程度等效,吸收速度不等效。控释片的达峰时间明显滞后普通制剂,该控释片显示出控释特征。
In this study, the pharmacokinetics of terazosin hydrochloride osmotic pump controlled release tablets in healthy volunteers were studied. Randomized crossover design was used to test the plasma concentration of terazosin hydrochloride in 20 healthy volunteers. The pharmacokinetic parameters were calculated by 3P97 software. The C_ (max) of common tablets (120.56 ± 23.15 ng / mL) was significantly higher than that of the controlled release tablets (95.27 ± 16.35 ng / mL) after oral administration of 4 mg tablets. The T max of controlled release tablets after oral administration was (2.65 ± 0.82) h, which was significantly lower than that of normal tablet (1.27 ± 0.61) h (P <0.05). The relative bioavailability (105.85 ± 6.12)%. The mean area under the curve (AUC_ (ss)) of the pharmacokinetic parameters after oral administration of common tablets and controlled release tablets were (1275.17 ± 175.35) and (1382.65 ± 205.31) ng · h / mL, respectively; max were (128.15 ± 22.37) and (98.57 ± 18.16) ng / mL, respectively; T max was 1.35 ± 0.71 and 2.76 ± 0.85 h, respectively; mean steady state blood concentration (C av) (53.13 ± 9.12) and (57.61 ± 9.25) ng / mL, respectively; the plasma concentration fluctuation (DF) were 2.25 ± 0.26% and 1.62 ± 0.25% respectively, and the relative bioavailability was (108.43 ± 6.26)%. The statistical tests showed that the AUC_ (0-48 h) and AUC_ (0-∞) of the two preparations were bioequivalent, that of the ordinary tablets and the controlled release tablets was equivalent to the oral dosage, and the absorption rate was not equivalent. The peak release time of the controlled release tablets obviously lagged behind that of ordinary preparations, which showed controlled release characteristics.