CAJ | 학술논문

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rhIL11浓度，血细胞计数仪计数血小板。iv和sc注射50～400 μg*kg-1后末端T1/2为2.8～3.6 h，AUC随剂量线性增加，全身清除率相近。sc生物利用度为0.68±0.15。多次给药时首次和第7次sc 注射后，除T1/2Ka延长(P＜0.05)外其它参数无明显改变。sc 400 μg*kg-1和200 μg*kg-1*d-1×7 d组血小板增高(P＜0.05 )。在研究剂量范围内，rhIL11呈线性药代动力学。血小板增高与给药剂量和次数有关，增高程度(血小板净增率×时间)与全身暴露强度(血药浓度×时间)呈正相关。
연구미후단차혹다차정맥주사(iv)화피하주사(sc)rhIL 11후약대동역학급주변혈소판계수변화。ELISA법검측혈청rhIL11농도，혈세포계수의 계수혈소판。iv화sc주사50～400 μg*kg-1후말단T1/2위2.8～3.6 h，AUC수 제량선성증가，전신청제솔상근。sc생물이용도위0.68±0.15。다차급약시수차화제7차sc 주사후，제T1/2Ka연장(P＜0.05)외기타삼수무명현개변。sc 400 μg*kg-1화200 μg*kg-1*d-1×7 d조혈소판증고(P＜0.05 )。재연구제량범위내，rhIL11정선성약대동역학。혈소판증고여급약제량화차 수유관，증고정도(혈소판정증솔×시간)여전신폭로강도(혈약농도×시간)정정상관。
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).