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目的:研究猕猴单次注射CHO细胞表达的重组人血小板生成素(rhTpo)后药动学及血小板计数变化.方法:酶联免疫吸附测定法(ELISA)检测血清中rhTpo含量.血细胞计数仪进行血小板计数.结果:rhTpo末端相半衰期(T12β)12-18h.各sc组间AUC依赖于剂量,而Cls相近.生物利用度050±018.rhTpo引起猕猴与剂量相关的血小板增加(平均增加率559%-1074%,P<005).增加峰值及持续天数与剂量有关.结论:rhTpo在猕猴体内表现为线性药动学.rhTpoT12β长与其分子量大,高度糖基化有关.血小板增加程度(血小板净增率×持续时间)与rhTpo全身暴露强度(血药浓度×时间)呈正相关.
Objective: To study the changes of pharmacokinetics and platelet count of recombinant human thrombopoietin (rhTpo) expressed in CHO cells of a single injection of macaque. Methods: The content of rhTpo in serum was detected by enzyme - linked immunosorbent assay (ELISA). Blood cell count for platelet count. Results: The half-life of rhTpo terminal phase (T12β) 12-18h. The AUCs for each sc group were dose-dependent and Cls were similar. Bioavailability 050 ± 018. RhTpo caused dose-related thrombocytosis in rhesus monkeys (mean rate of increase 559% -1074%, P <005). Increase the peak and the number of days and dose-related. Conclusion: rhTpo appears as a linear pharmacokinetic in rhesus monkeys. The long rhTpoT12β is associated with its high molecular weight and high glycosylation. The extent of thrombocytopenia (net increase in platelets × duration) was positively correlated with the systemic exposure to rhTpo (plasma concentration × time).