染料木素在健康受试者中的尿排泄动力学

Pharmacokinetics of genistein in urine of healthy volunteers

为了研究人体口服染料木素胶囊(雌激素类药物)的尿排泄规律,筛选30名健康受试者按平行设计口服染料木素50、100和300 mg,采用LC-MS/MS法测定各时段尿液中的染料木素,并结合酶解法间接测定其葡糖醛酸结合物(glucuronidated genistein,GENG),以DAS2.0程序计算尿药动力学参数。结果表明,尿液中原药浓度很低,含量少于GENG的1%,其3个剂量的48 h平均累积尿排量分别为0.037、0.134和0.142 mg,累积尿排率仅分别为给药剂量的0.07%、0.13%和0.05%。而GENG的含量较高,其48 h累积尿排泄量分别为5.3、13.8和15.4 mg,累积尿排率分别为10.6%、13.8%和5.1%,最大尿排速率分别为0.4、1.0和1.4 mg·h-1(tmax为6 h)。研究证明,部分药物在人体内以GENG形式经尿液排泄,而GENG的累积排泄量和最大尿排速率在50～100 mg内随剂量倍比递增,在300 mg时呈非线性递增。

In order to study the excretion of genistein （GEN） capsule, an estrogen drugs, in human, 30 healthy volunteers were selected and orally administered 50, 100, and 300 mg genistein in an parallel study. Genistein were determined in urine by LC-MS/MS and glucuronidated genistein （GENG） were indirectly determined with enzymatic hydrolysis in urine by LC-MS/MS, and the pharmacokinetic parameters were analyzed by DAS software （vet 2.0）. The result showed that the concentrations of genistein in human urine were less than 1% of the GENG, and the cumulative excretion of GEN in 48 h were 0.037, 0.134, and 0.142 rag, separately, and the urinary excretion percentage were only 0.07%, 0.13%, and 0.05%, separately. But the cumulative excretion of GENG in 48 h was 5.3, 13.8, and 15.4 mg, separately, and the urinary excretion percentage were 10.6%, 13.8%, and 5.1%, separately, and the max urinary excretive rate was 0.4, 1.0, and 1.4 mg ·h^-1, separately （tmax were 6 h）. Studies showed that part of drug excreted through kidney in a form of GENG in human, and the cumulative urinary excretion and the maximum excretion rate of GENG showed a proportional increase conditioned with the dose in the range of 50-100 mg, but showed non-linear increase feature in 300 m