乌拉地尔缓释胶囊相对生物利用度和体内外相关性研究

 目的　对乌拉地尔缓释胶囊进行相对生物利用度和体内外相关性研究。方法　采用反相高效液相色谱法测定24名健康志愿受试者单剂量和多剂量口服乌拉地尔缓释胶囊供试制剂与参比制剂后乌拉地尔血药浓度的变化。用3P97药动学程序处理试验数据,并对试验结果进行方差分析和双单侧t检验;体外释放度采用中国药典2000版二部的转篮法。结果 单剂量试验乌拉地尔的相对生物利用度为:(96.37±13.77)%;两种制剂乌拉地尔的药-时曲线下面积(AUC_0→t)分别为:(2347.6±493.2),(2458.9±526.5 )ng·h·mL^-1;达峰时间(t_max)分别为:(4.17±0.28),(4.23±0.29)h;峰浓度(c_max)分别为:(325.6±40.3),(322.0±75.5 )ng·mL^-1。多剂量试验乌拉地尔的相对生物利用度为:(99.99±16.24)%;两种制剂乌拉地尔的药-时曲线下面积(AUC_0→t)分别为:(4513.1±1372.7) ,(4549.7±1308.8)ng·h·mL^-1;稳态达峰时间(t_max)分别为:(4.00± 0.49),(4.08±0.43)h;稳态峰浓度(c_max)分别是 :(544.5±147.1),(565.7±146.8)ng·mL^-1;波动度DF分别是(91.22±14.07)%,(84.53±26.10)%。体外12h平均累积释放86.33%和87.35%。结论　对单剂量口服两种制剂后的lnAUC_0→∞,lnAUC_0→t,lnc_max经双单侧t检验，t_max经秩和检验进行生物等效性评价，表明两者为生物等效制剂，且乌拉地尔缓释胶囊的体内吸收与体外释药有良好的相关性(P<0.05)。

Relative bioavailability and the correlation study on urapidil sustained-release capsules between in vitro and in vivo

OBJECTIVE To investigate the relative bioavailability and the correlation study on urapidil sustained release capsules between in vitro and in vivo.METHODS Urapidil concentration in plasma was detected by RP-HPLC after twenty four healthy male volunteers were treated with a single dose and multiple doses of oral urapidil sustained release capsules test and reference preparations.The data was calculated with 3P97 program.The results were analyzed by ANOVA and two one-side test. The dissolution of urapidil was determined in vitro according to CP(2000ed,partII).RESULTS The relative bioavailability of urapidil in the single dose treatment was (96.37±13.77)%AUC _0-t of urapidil test and reference preparations were (2347.6±493.2)ng·h·mL^-1 versus (2458.9±526.5) ng·h·mL^-1;t_maxwere (4.17±0.28) h versus (4.23±0.29)h;c_maxwere(325.6±40.3) ng·mL^-1 versus (322.0±75.5)ng·mL^-1.The relative bioavailability of urapidil in the multiple dose treatment was (99.99±16.24)%.AUC_0→tof urapidil test and reference preparation were (4513.1±1372.7)ng·h·mL^-1 versus (4549.7±1308.8)ng·h·mL^-1,t_maxwere(4.00±0.49)h(4.08±0.43)h,c_maxwere(544.5±147.1)ng·mL^-1 versus (565.7±146.8)ng·mL^-1,DF were (91.22±14.07)% versus (84.53±26.10)%.The dissolution of urapidil in the two preparations was 86.33% and 87.35% within 12h, respectively.CONCLUSION Bioequivalent evaluation of two preparations by two one side test and rank sum test showed that the two preparations were bioequivalent. There was a significant relationship between absorption in vivo and dissolution in vitro (P<0.05).