恒河猴肌注新型重组人肿瘤坏死因子的药代动力学

Pharmacokinetic study of new recombinant human tumor necrosis factor al pha in rhesus monkey

目的 研究新型重组人肿瘤坏死因子 (nrh TNFα)在恒河猴体内的药代动力学行为 .方法 采用 EL ISA法测定恒河猴 im nrh TNFα后的血药浓度 .结果 恒河猴按 40 μg·kg- 1 剂量 im nrh TNFα后 ,血液中的平均达峰时间为 1.7h;峰浓度的个体差异较大 ,范围为 5 75～ 112 0 ng· L- 1 ,平均峰浓度为 833ng· L- 1 ;药物在血液中的消除符合一房室模型 ,半衰期 T1 / 2 为 1.4～ 2 .4(平均 1.9) h.结论 nrh TNFα im后 ,能被恒河猴吸入血 ,在血液中的消除符合一房室模型 ,在灵长类动物恒河猴的药代动力学行为与啮齿类动物小鼠的相类似 。

AIM To study the pharmacokinetics of nrhTNFα in rhesus monkey. METHODS The concentration of nrhTNFα in serum was measured by ELISA after im injection. RESULTS Mean time of reaching peak serum concentration was 1.7 h, after the rhesus monkey was injected in im 40 μg·kg -1 nrhTNFα. The levels of peak concentration vary greatly between individuals, ranging from 575 to 1120 ng·L -1, with the mean peak concentration of 833 ng·L -1. The clearance of nrhTNFα in blood accorded with atrioventricular models. The half l ife(T 1/2) was from 1.4 to 2.4 h and the mean time was 1.9 h. CONCLUSION nrhTNFα can be absorbed in blood of the rhesus monkey af ter injection by im and its clearnce accorded with atrioventricular models. The pharmacokinetics of nrhTNFα is analogy betwee n the rhesus monkey and mice, but the absorption and the clearance in blood after injection are slower in rhesus monk eys than in mice.