max和藥時(shí)曲線下面積AUC(0-24h)、AUC(0-∞)均隨給藥劑量的增加而增大,Cmax、AUC(0-24h)和AUC(0-∞)三者均與劑量呈線性相關(guān),各劑量組t1/2Z、Tmax、CLz和Vz均較為一致。與單次給藥相比,食蟹猴多次sc給藥后的t1/2z有所延長(zhǎng)但其他主要PK參數(shù)(Tmax、Vz和CLz等)均較為一致,多次給藥后,體內(nèi)藥物無(wú)蓄積傾向。結(jié)論 食蟹猴單次sc FGF-21后,在150~600 μg/kg劑量范圍內(nèi)呈現(xiàn)線性動(dòng)力學(xué)特征。單次與多次sc給予FGF-21后,兩者的PK行為特征基本一致,無(wú)明顯藥物蓄積。;Objective The pharmacokinetic profile of recombinant human fibroblastgrowth factor-21(FGF-21) for injection after single and multiple subcutaneous administration in cynomolgus monkeys was studied. Methods 18 cynomolgus monkeys were administered subcutaneously at single dose of 150, 300, 600 μg/kg FGF-21 or multiple dose of 300 μg/kg in a randomized design, parallel and dose-escalation study. ELISA method was developed to determine the dynamic changes of drug concentration in serum, and pharmacokinetic parameters were calculated by using DAS 3.2.4 pharmacokinetics program. Results Pharmacokinetic parameters in cynomolgus monkeys between different single dose groups are as follows:Cmax, AUC(0-24 h) and AUC(0-∞) were positively proportional linear related with increasing dose.t1/2Z, Tmax, CLz, and Vz were all consistent in each dose groups. Compared with single administration, the t1/2z of cynomolgus monkeys was prolonged after multiple administrations, but other major PK parameters (Tmax, Vz, CLz) were consistent. After repeated administration, there was no accumulation tendency of drugs in body. Conclusion FGF-21 administered subcutaneously at single dose of 150-600 μg/kg in cynomolgus monkeys exhibits linear pharmacokinetics. The characteristics of pharmacokinetics are basically consistent with single and multiple dose of 300 μg/kg FGF-21, indicating that no significant drug accumulation was ovserved."/>