不同剂量RT-A灌胃给药后其活性代谢产物RT-B在大鼠体内的药动学

Pharmacokinetics of the active metabolite RT-B in rat plasma after oral administration of a new compound RT-A at different doses

目的研究大鼠分别以60、120、240 mg.kg-1剂量灌胃给予I类新药RT-A后,其活性代谢产物RT-B的药动学。方法采用RP-HPLC法测定RT-B在大鼠体内的血药浓度,用DASS2.0药物动力学程序求算其药动学参数。结果主要药动学参数为:tmax分别为(18.000±0.000)、(18.000±1.265)、(18.000±0.000)h,ρmax分别为(3.270±0.563)、(5.772±1.287)、(8.525±1.173)mg.L-1,AUC(0→t)分别为(69.881±11.561)、(107.913±16.591)、(165.181±21.411)mg.h.L-1,AUC(0→∞)分别为(71.843±12.454)、(109.894±15.278)、(173.847±24.602)mg.h.L-1,t1/2分别为(10.276±1.797)、(9.641±1.961)、(11.210±2.985)h。结论RT-B在大鼠体内呈二室模型分布,药时曲线呈现双峰,药时曲线下面积与给药剂量呈线性正相关。

Objective To study pharmacokinetic characteristic of the active metabolite 3,4,5-tri （2-carboxy- methoxy） -stilbene （ RT-B ） after intragastric administration of a new compound 3,4,5-tri （ 2-ethoxycarbonyle thoxy） stilbene （RT-A） at different doses of 60,120, and 240 mg. kg - 1. Methods The reversed-phase high- performance liquid chromatography was applied to monitor the plasma concentration of RT-B. The pharmacokinetic parameters were estimated by the DASS2.0 computer program. Results The main pharmarcokinetic parameters of RT-B were as follows： tmax were （ 18. 000 ±0. 000）, （ 18. 000 ± 1. 265 ） and （ 18. 000± 0.000 ） h ;ρmax were（3. 270± 0.563 ）, （5. 772±1. 287 ） and （8. 525± 1. 173 ）mg. L-1 ; AUC（0→t）were （69. 881±11.561）, （107.913 ± 16. 591） and（ 165. 181 ±21. 411 ） mg·h·L-1 ; AUC（0→∞） were（71. 843 ±12.454）, （ 109. 894 ± 15. 278 ） and （ 173. 847± 24. 602） mg. h. L -1 ; t1/2 were （ 10.276±1. 797 ）, （ 9.641 ± 1.961 ） and （ 11. 210 ±2.985 ） h ,respectively. Conclusions The time-concentration curve of RT-B is corresponded to the two-compartment model. Two peaks are shown in mean plasma concentration-time profile. The AUC of RT- B is linear up with the increasing of the RT-A dose by intragastric administration.