单次静滴人参皂苷-Rd注射液在中国健康志愿者的药代动力学及耐受性

Pharmacokinetics and tolerance of single dose intravenous drip of ginsenoside-Rd injection in Chinese healthy volunteers

目的研究中国健康志愿者单次静滴人参皂苷-Rd（防治脑缺血中药）注射液的药代动力学及耐受性。方法选12名健康志愿者,按双拉丁方设计分组,每位受试者于3个周期内交叉静脉滴注人参皂苷-Rd注射液10、40、75 mg 3个剂量;用LC/MS/MS法测定血浆人参皂苷-Rd浓度,用DAS软件计算药代动力学参数;试验过程中密切观察药物不良反应。结果3个剂量（10、40、75 mg）的主要药代动力学参数：Cm ax分别为（2.84±0.47）、（10.48±1.74）、（19.34±2.62）mg.L-1,t1/2分别为（19.29±3.44）、（18.41±2.92）、（17.67±2.01）h,AUC0-t分别为（27.26±8.12）、（112.62±24.08）、（208.36±51.36）mg.L-1.h-1,Cm ax、AUC0-t与剂量的线性关系良好,随给药剂量的增加基本成比例增加。试验过程中未出现严重不良事件。结论该药在中国健康受试者的体内过程符合线性药代动力学特征,剂量在10-75 mg内较安全。

Objective To study the pharmacokinetics and safety of single dose intravenous drip of ginsenoside-Rd injection in Chinese healthy volunteers. Method Twelve healthy volunteers were enrolled and grouped by latin square design, each of whom was administered with single dose intravenous drip of 10 mg, 40 mg, and 75 mg ginsenoside-Rd injection in 3 cross periods. The plasma concentrations of ginsenoside-Rd were determined with LC/MS/MS and the pharmacokinetic parameters were calculated with DAS software. Throughout the trial process adverse events were monitored closely. Results The main pharmacokinetic parameters of the volunteers administered with single dose intravenous drip of 10 mg, 40 mg, and 75 mg ginsenoside-Rd injection are calculated as follows, respectively. Cmax were （ 2. 84 ± 0. 47 ）, （ 10. 48 ± 1.74 ）, （ 19.34 ± 2.62） mg · L^-1 ; t1/2 were （ 19.29 ±3.44）, （18.41 ±2.92）, （ 17.67 ± 2.01 ） h ; AUC0-t were （27.26 ± 8. 12）, （ 112. 62 ± 24. 08 ）, （208.36 ±51.36） mg · L^-1 · h^-1. Among the parameters, Cmax and AUC0-t show good linearity with the dosages and increase in proportion to the dosage. No severe adverse events were observed thoughout the trial process. Conclusion Single dose intravenous drip of ginsenoside-Rd injection in Chinese healthy volunteers fits the linear pharmacokinetic characteristics and is safe with the dosage ranged from 10 mg to 75 mg.