栀子大黄汤配伍变化对栀子中京尼平苷药动学的影响

目的：通过测定栀子、栀子-大黄、栀子-大黄-枳实和栀子大黄汤4种汤剂中京尼平苷在大鼠体内的药动学参数，考察栀子大黄汤配伍的变化对栀子中京尼平苷药动学的影响。方法：将SD大鼠随机分为4组，分别灌胃给予栀子、栀子-大黄、栀子-大黄-枳实、栀子大黄汤汤剂7．7、6．9、7．3、8．2mL·kg^-1，采用HPLC法测定各汤剂给药后5、10、20、30、60、90、120、240、360和480分钟时的血药浓度，并用BAPP2．0软件计算药动学参数。结果：栀子、栀子-大黄、栀子-大黄-枳实和栀子大黄汤组中京尼平苷的Gmax分别为（2．47±0．47）、（2．15±0．49）、（3．95±0．18）、（3．31±0．86）mg·L^-1；t1／2分别为（163±24）、（176±14）、（282±16）、（227±41）min；AUC0-t分别为（369±38）、（348±61）、（814±74）、（549±58）mg·L^-1·min^-1。与栀子组相比，栀子-大黄组中京尼平苷的Cmax和AUC0-t略有下降，栀子-大黄-枳实组和栀子大黄汤组中京尼平苷的Cmax和AUC0-t均显著升高，但栀子大黄汤组中京尼平苷的AUC0-t显著低于栀子-大黄-枳实组（P〈0．05）。结论：栀子大黄汤药材不同配伍对京尼平苷的药动学存在不同的影响，大黄可使京尼平苷的生物利用度略微下降，枳实可显著增加京尼平苷的生物利用度，淡豆豉则可显著降低京尼平苷的生物利用度。

Effect of Different Formula Compatibility of Zhi-Zi-Da-Huang Decoction on the Pharmacokinetics of Geniposide in Gardenia jasminoides

Objective： To obtain pharmacokinetics parameters from concentration-time data of geniposide in different recipes of Zhi-Zi-Da-Huang decoction （ZZDHD） which contains Gardenia jasminoides （ZZ）, Rheum officirtale （DH）, Citrus aurantium （ZS） and Semen Sojae Preparatum （DDC）, including ZZ, ZZ-DH, ZZ-DH-ZS and ZZDHD. And then to investigate the effect of the different recipes of ZZDHD on the pharmaeokineties of geniposide. Methods： Twenty-four rats were randomly divided into four groups, and were administered ZZ （7. 7 mL. kg^-1）, ZZ-DH （ 6. 9 mL- kg^-1）, ZZ-DH-ZS （ 7.3 mL- kg^-1） and ZZDHD（ 8.2 mL. kg ^- 1）, respectively. The plasma concentrations of four recipes at 5, 10, 20, 30, 60, 90, 120, 240, 360 and 480 min were determined by HPLC, and the pharmacokinetics parameters of geniposide in these recipes were consequently computed by software program BAPP2.0. Results： The main pharmacokinetics parameters of geniposide in ZZ, ZZ-DH, ZZ-DH-ZS and ZZDHD were as follows： Cmax was （ 2.47 ± 0.47）, （ 2.15 ±0.49）, （ 3.95 ± 0.18）, （ 3.31± 0. 86） mg. L^-1, respectively, t1/2 was （ 163± 24）, （ 176 ± 14）, （282 ± 16）, （227±41） min, respectively, AUC0-t, was （369±38）, （348 ±61）, （814 ± 74）, （549±58） mg.L^-1.min^-1, respectively. Cmax and AUC0-t of geniposide decreased in ZZ-DH group, and increased statisticsly in ZZ-DH-ZS and ZZDHD groups compared with ZZ group （P 〈 0. 05）. However, AUC0-t of geniposide decreased in ZZDHD group compared with ZZ-DH-ZS group （ P 〈 0. 05）. Conclusion： Different recipes of ZZDHD had different impact on the pharmacokinetics of geniposide. The bioavailability of geniposide can be lowered by DH and DDC, but can be elevated by ZS.