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


CONCLUSIONS
rhTpo behaved as a linear pharmacokinetics in the monkey within dose range of 0.5-8 micrograms.kg-1.
Song
H F
HF
Department of Pharmacology, Academy of Military Medical Sciences, Beijing, China.
Liu
X W
XW
Tang
Z M
ZM
D000818:Animals; D019540:Area Under Curve; D005260:Female; D008253:Macaca mulatta; D008297:Male; D010976:Platelet Count; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013926:Thrombopoietin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D011994:Recombinant Proteins; D013926:Thrombopoietin