Pharmacokinetics and peripheral platelet counts after a single dose of recombinant human thrombopoietin in rhesus monkeys
Abstract
AIM:
To study the pharmacokinetics and the change of peripheral platelet counts after a single dose of recombinant human thrombopoietin (rhTpo).
METHODS:
After i.v. or s.c. injections of rhTpo in 12 rhesus monkeys, rhTpo concentration 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 s.c. were linearly increased with dose, while Cls were 0.061, 0.08, and 0.07 L.kg-1.h-1 in s.c. 0.5, 2, and 8 micrograms.kg-1 groups, respectively. Bioavailability was 0.50 +/- 0.18 after s.c. 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 the sustained days of platelet increase were dose-related. The degree of platelet increase (% x time) correlated with the systemic exposure to rhTpo (C x time).
CONCLUSION:
rhTpo behaved as a linear pharmacokinetics in the monkey within dose range of 0.5-8 micrograms.kg-1.
Keywords:
To study the pharmacokinetics and the change of peripheral platelet counts after a single dose of recombinant human thrombopoietin (rhTpo).
METHODS:
After i.v. or s.c. injections of rhTpo in 12 rhesus monkeys, rhTpo concentration 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 s.c. were linearly increased with dose, while Cls were 0.061, 0.08, and 0.07 L.kg-1.h-1 in s.c. 0.5, 2, and 8 micrograms.kg-1 groups, respectively. Bioavailability was 0.50 +/- 0.18 after s.c. 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 the sustained days of platelet increase were dose-related. The degree of platelet increase (% x time) correlated with the systemic exposure to rhTpo (C x time).
CONCLUSION:
rhTpo behaved as a linear pharmacokinetics in the monkey within dose range of 0.5-8 micrograms.kg-1.