Pharmacokinetics and peripheral platelet counts after a single dose of recombinant human thrombopoietin in rhesus monkeys

AIM: To study the pharmacokinetics and the change of peripheral platelet co unts after a single dose of recombinant human thrombopoietin (rhTpo). METHO DS: After iv or sc injections of rhTpo in 12 rhesus monkeys, rhTpo concentr ation in serum was determined by ELISA. Platelets were counted by automatic microcell counter. RESULTS: The terminal half-lives of rhTpo were 12 - 18 h. AUC following sc were linearly increased with dose, while CI, were 0.061 , 0.08, and 0.07 L.kg<SUP>-1</SUP>.h<SUP>-1</SUP> in sc 0.5, 2, and 8 mu g. kg<SUP>-1</SUP> groups, respectively. Bioavailability was 0.50 +/- 0. 18 af ter sc. Single dose of rhTpo was associated with an increase in platelets ( 55.9% - 107.4%, P < 0.05) in a dose-related manner. The peak response and t he sustained days of platelet increase were dose-related. The degree of pla telet increase (% x time) correlated with the systemic exposure to rhTpo (C x time). CONCLUSION: rhTpo behaved as a linear pharmacokinetics in the mon key within dose range of 0.5 - 8 mu g.kg<SUP>-1</SUP>.<SUP></SUP>