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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 the pharmacokinetics of the active metabolite RT-B after intragastric administration of a novel drug RT-A at doses of 60, 120 and 240 mg.kg-1 in rats. Methods The plasma concentrations of RT-B in rats were determined by RP-HPLC. The pharmacokinetic parameters were calculated by DASS2.0 pharmacokinetic program. Results The main pharmacokinetic parameters were as follows: tmax were (18.000 ± 0.000), (18.000 ± 1.265) and (18.000 ± 0.000) h, respectively, and pmax were (3.270 ± 0.563), (5.772 ± 1.287) and (8.525 ± 1.173) The AUC (0 → ∞) were (69.881 ± 11.561), (107.913 ± 16.591), (165.181 ± 21.411) mg.hL-1 and (71.843 ± 12.454) , (109.894 ± 15.278) and (173.847 ± 24.602) mg.hL-1 respectively, and the values of t 1/2 were (10.276 ± 1.797), (9.641 ± 1.961) and (11.210 ± 2.985) h, respectively. Conclusion RT-B is distributed in two-compartment model in rats. The curve of drug-use time is bimodal. The area under the curve of drug-loading time is linearly and positively correlated with the dosage of RT-B.