猕猴单次及多次注射重组人白介素—11后的药代动力学及外周血小板计数变化

研究猕猴单次或多次静脉注射(iv)和皮下注射(sc)rhIL-11后药代动力学及周边血小板计数变化。ELISA法检测血清rhIL-11浓度，血细胞计数仪计数血小板。iv和sc注射50～400μg

Pharmacokinetics and peripheral platelet counts after single or multidosing of recombinant human interleukin11 in rhesus monkeys

The pharmacokinetics and changes of peripheral plat elet counts following single or multidosing of recombinant human interleukin 11(rhIL11) in rhesus monkdy were studied. Single dosage regime included iv of 100 μg*kg-1，or sc of 50,100, or 400 μg*kg-1; and multidosing regime was sc of 200 μg*kg-1*d-1×7 d. The concentration in serum was determined by ELISA. Platelet counts were assayed by automatic microcell co unter. The average terminal halflives was almost the same in four sc groups(3. 6～3.7 h), and was shorter after iv (2.8±0.4 h, P＞0.05), Areas und er concentrationtime curves (AUC)were linearly increased with dose(r=0 .97, n=4, P＜0.05), while CLs was no statistical difference. Bioav ailability after sc was 0.68±0.15. The concentrations determined after mult id osing were near to the levels predicted by pharmacokinetic parameters estimated after the first dosing. The pharmacokinetic parameter after the 7th dosing was similar to lst dosing, except T1/2 Ka was significantly prolong ed (P＜0.05). Remarkable increase of platelets(P＜0.05) was observed after sc 400 μg*kg-1 and 200 μg*kg-1*d-1×7 d. The maximal response was at day 8～9 and returned to normal at day 16～18. Li near pharmacokinetics was observed in monkey after single or multidosing regim e within the dose range of 50～400 μg*kg-1. The degree of platelet incre ase(%×T)was depended both on dose and repeatinjectedtimes, which correlated with the systemic exposure to rhIL11(C×T).