帕拉米韦三水合物氯化钠在健康人体的药代动力学

Pharmacokinetics of peramivir trihydrate and sodium chloride in Chinese healthy volunteers

目的研究帕拉米韦三水合物氯化钠注射液在中国健康人体的药代动力学。方法 30名健康志愿者分为150,300,600 mg 3个剂量组,单次或多次静脉滴注帕拉米韦三水合物氯化钠注射液后,用HPLC-MS/MS法测定血浆和尿液中帕拉米韦的浓度,用WinNonLin 5.0计算主要药代动力学参数。结果健康受试者单次静脉滴注试验药物150,300和600 mg后,帕拉米韦的主要药代动力学参数:c max分别为(10.95±1.98),(20.50±2.08),(44.22±7.00)μg·mL-1;V分别为(30.54±7.24),(36.36±5.40),(36.45±14.29)L;CL分别为(7.58±1.30),(7.02±0.94),(6.29±0.75)L·h-1;AUC0-t分别为(20.28±3.72),(43.54±7.79),(96.47±11.42)μg·mL-1·h。24 h尿液中帕拉米韦的累积排泄百分率(Ae)分别为(72.20±22.10)%,(82.25±11.61)%,(82.00±8.46)%。健康受试者多次静脉滴注试验药物150和300 mg后,帕拉米韦的主要药代动力学参数:cmax,ss分别为(10.48±1.28),(20.19±2.73)μg·mL-1;CL ss分别为(7.92±1.04),(6.88±0.94)L·h-1;AUC0-t分别为(19.25±2.94),(44.40±6.41)μg·mL-1·h。蓄积率分别为(1.03±0.03)%,(1.03±0.02)%;Ae分别为(70.98±15.91)%,(73.39±10.94)%。结论静脉滴注帕拉米韦三水合物氯化钠注射液150～600 mg,在中国健康志愿者的体内过程未明显偏离线性药代动力学特征,每天1次连续给药在体内无蓄积,试验药物主要以原型从尿中排出。

Objective To study the pharmacokinetics of peramivir trihy- drate and sodium chloride injection in Chinese healthy volunteers. Methods Thirty healthy volunteers were enrolled and administered with single or multiple doses of 150, 300 or 600 mg peramivir trihydrate and sodium chloride injection by intravenous drip infusion （ n = 10 for each dose lev- el）. The concentrations of peramivir in human plasma and urine were determined by HPLC - MS/MS. The main pharmacokinetic parameters were calculated with WinNonLin 5.0 software. Results The main pharmacokinetic parameters of peramivir after single dose of 150, 300 and 600 mg peramivir trihydrate and sodium chloride injection were as follows：Cmax were（10. 95 ± 1.98）, （20.50±2.08）, （44. 22 ±7.00）μg·mL^-1 ; V were（30. 54 ±7.24）, （36.36 ± 5.40）, （36.45 ± 14.29） L; CL were （7.58 ±1.30）, （7.02 ±0.94） ,（6.29±0.75）L. h^-1;AUC0-t,were （20.28±3.72）,（43.54 ±7.79）,（96.47 ±11.42）μg·mL^-1·h;accumulative urine excretion rate of 24 h （ Ae% ） were （72.20 ± 22. 10） %, （ 82.25 ± 11.61 ） %, （ 82.00 ±8.46 ） %, respectively. The main pharmacokinetic parameters of peramivir after multiple dose of 150 and 300 mg peramivir trihydrate and sodium chloride injection were as follows ： c were （ 10. 48 ±1.28 ）, （ 20. 19 ± 2. 73 ） μg·mL^-1 ; AUC0 -t were （ 19.25 ± 2. 94）, （44.40 ±6. 41 ）μg·mL^-1·h ; CLss were （ 7.92 ± 1.04 ） , （ 6. 88 ± 0. 94 ） L · h - 1 ; accumulation ratio were （ 1.03 ± 0. 03 ）, （ 1.03 ± 0. 02 ） ; A e were （70. 98± 15.91 ） %, （73.39 ± 10. 94 ） %, respectively. Conclusion The process of peramivir in the dosage range of 150 - 600 mg dose not show any significant departure from linear dynamic feature. There is no accumulation after multiple dosing. Peramivir is mainly eliminated from urine in parent drug.