目的 研究肾病综合征（nephrotic syndrome，NS）大鼠体内雷公藤多苷片（Tripterygium Glycosides Tablets，GTW）和袢利尿剂呋塞米（furosemide，FSM）单独及合用后的药动学变化特征，为临床合理用药提供参考。方法 采用尾iv多柔比星诱导NS模型大鼠，单独及联合ig GTW和FSM，进行血药浓度测定，绘制药时曲线并计算药动学参数；并观察单独及联合ig GTW和FSM对NS模型大鼠肝肾功能、血脂、肾脏病理学及肾脏有机阴离子转运蛋白（organic anion transporters，OATs）的影响。结果 与对照组比较，NS大鼠体内GTW生物碱类成分暴露升高，FSM暴露降低；肌酐、白蛋白、血脂差异显著（P＜0.05），OATs表达下降，肾脏病理学显示组织受损。经过GTW及FSM治疗后，生化指标血肌酐明显好转，OATs表达有所恢复，合用后FSM的体内暴露有所回升，GTW成分体内暴露的降低。结论 药动学/药效学结果证明了2药正常剂量合用对NS的治疗效果，其总体安全性较好。建议临床实践中，关注患者的肝肾功能，把控GTW的使用剂量和频率，对症使用FSM，促进2药合理联用。

Objective To study the pharmacokinetics of Tripterygium Glycosides Tablets (雷公藤多苷片, GTW) and furosemide (FSM) alone and in combination in rats with nephrotic syndrome (NS), and the therapeutic effect of GTW, so as to provide references for clinical rational drug use. Methods NS model rats were induced by intravenous injection of doxorubicin, rats were individual and combined ig GTW and FSM. Blood drug concentration was determined, the concentration-time curves and pharmacokinetic parameters were calculated. The effects of ig GTW and FSM alone and in combination on liver and kidney function, blood lipids, renal pathology and organic anion transporters (OATs) in NS model rats were observed. Results Compared with control group, exposure of GTW alkaloids was increased and exposure of FSM was decreased in NS rats. Plasma creatinine, plasma albumin and lipid levels were significantly different (P < 0.05) between two groups. OATs expression was decreased, renal pathology showed tissue damage. After GTW and FSM treatment, biochemical indexes such as creatinine and the expressions of OATs were improved, and the exposure of FSM was also increased, the exposure of GTW components was decreased. Conclusion The pharmacokinetic/pharmacodynamic results have demonstrated the therapeutic effect of the combination of two drugs at normal doses on NS had overall good safety. It is recommended to pay attention to the liver and kidney function of patients in clinical practice, control the dosage and frequency of GTW use, use FSM symptomatically, and promote the rational combination of the two drugs.

R285.61

国家自然科学基金青年科学基金项目（81703861）