摘要
目的:研究大黄酸羧基酯化对其在大鼠体内药动行为的影响。方法:采用大黄酸甲酯和大黄酸乙酯作为模型药, 大黄酸作为阳性对照, 对大鼠单次灌胃70 mg·kg-1或者单次静注 0.7 mg·kg-1, HPLC 荧光同时监测大鼠血浆中三种分析物的血浓经时变化。结果:大黄酸甲酯和大黄酸乙酯灌胃和静注给予大鼠后, 血浆中均测不到酯类原型, 但能测到一定量的大黄酸。将甲酯和乙酯衍生物灌胃后在大鼠血浆中所测得的大黄酸成分的经时变化与直接灌胃大黄酸后大鼠血浆中大黄酸成分的经时过程相比较, 其主要的药动参数分别为:cmax (0.058 ± 0.035)、(0.95 ± 0.090)、(42.66 ± 14.41) mg·L-1; Tmax (6.7 ± 2.3)、(10.7 ± 2.3)、(0.9 ± 0.1) h; t1/2β (6.0 ± 1.7)、(6.4 ± 1.0)、(3.2 ± 0.6) h; AUC0-∞ (1.03 ± 0.76)、(12.79 ± 0.96)、(80.28 ± 13.59) h·mg·L-1。结论:羧基酯化降低了大黄酸在大鼠体内的有效暴露剂量, 提示此类衍生物不适于作为大黄酸的前体药物进行开发。
AIM： To explore the effects of carboxyl-esterification on pharmacokinetics of rhein in rat. METHODS： Rhein methylate （REM） and Rhein ethylate （REE） were used as model drugs while rhein （RE） as a positive control. The simultaneous detec- tion of three analytes in rat plasma samples was carried out by an HPLC-fluorescence method. Single dose of RE, REM or REE was administered to rats by both ig route at 70 mg.kg-1 and iv route at 0.7 mg.kg-1. RESULTS： REM and REE were entirely metabolized to rhein after ig and iv administration of either REE or REM to rats and only rhein was detected in plasma. Therefore, the pharmacoki- netic comparisons among RE, REE and REM in rat were carried out based on the profiles of rhein in rat plasma after the administration of each compound. The main pharmacokinetic parameters of REM, REE and RE after ig administration were as follows： Cmax （0.058 ± 0.035）, （0.95 ± 0.090）, （42.66± 14.41） mg.L-1; Tmax （6.7 ± 2.3）, （10.7 ± 2.3）, （0.9 ± 0.1） h; tl/2β（6.0 ± 1.7）, （6.4 ± 1.0）, （3.2 ± 0.6） h; AUCo-∞ （1.03 ± 0.76）, （12.79± 0.96）, （80.28 ±13.59） h.mg.L-1. CONCLUSION： It was found that the reconstruction of carboxyl - esterification has significantly reduced the net exposure amount of rhein in vivo, leading to its inaptitude in the development of drug precursors of rhein.
出处
《中国天然药物》
SCIE
CAS
CSCD
北大核心
2009年第3期228-233,共6页
基金
supported by the National‘863’Projects ( No. 2002AA2Z3 113
No. 2003AA2Z347A
No. 2005AA2Z3C70 )
the Key Lab of Drug Metabolism and Phar-macokinetics of Jiangsu Province( No. BM2001201)~~
