酶联免疫法研究注射用重组人胸腺肽α1的猕猴药动学

Pharmacokinetics of rh-Tα1 for injection in monkeys by enzyme-linked immunosorbent assay

目的:研究猕猴单次sc重组人胸腺肽α1(rh-Tα1)的药动学。方法:6只猕猴单次scrh-Tα1350μg/kg,采用酶联免疫分析检测(ELISA)法测定动物的血药浓度,实验数据用3P97药代软件拟合并计算药动学参数。结果:rh-Tα1在猕猴体内的消除符合一房室模型,6只动物的达峰时间(tmax)均为1.5h,平均消除半衰期(t1/2ke)为(2.9±0.8)h;峰浓度(Cmax)均值为(297.0±43.3)ng/mL;平均清除率(CL)为(0.373±0.116)mL/(h·kg);药时曲线下面积(AUC0～24h)均值为(1165±333)ng·h/mL。结论:血清样品经5倍稀释后用ELISA方法能较准确测定猕猴血清中rh-Tα1的量。6只猕猴scrh-Tα1后达峰时间一致且较短,主要药动学参数显示一定个体差异,但无明显性别差异。

Objective: To explore pharmacokinetic properties of a recombinant human Thymosin α1 (rh-Tα1) followingsc administration in monkeys. Methods: The monkeys received single sc doses of rh-Tα1 at 350 μg/kg. Serum concentration of rh-Tα1 was measured at various time-points after dosing by an enzyme-linked immunosorbent assay (ELISA). Pharmacokinetic parameters were calculated with 3P97 software. Results: The concentration-time profile of rh-Tα1 in monkeys was described by an one-compartment model. The mean time to reach peak concentration (tmax) was 1.5 h. The mean elimination half-life (t1/2ke) was (2.9 ± 0.8) h. The average clearance rate was (0.373 ± 0.116) mL/(h·kg). The mean peak concentration (Cmax) was (297.0 ± 43.3)ng/mL. The mean area under the serum concentration-time curve (AUC0~24 h) was (1 165 ± 333) ng·h/mL. Conclusion: Serum concentration of rh-Tα1 is detected accurately by ELISA method when serum samples are diluted five times. The tmax of the six monkeys are the same, but the main pharmacokinetic parameters demonstrate a certain degree of individual differences without obvious sex differences.