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目的研究抗肿瘤坏死因子-α(TNF-α)全人源单抗在食蟹猴体内的药代动力学特征及生物利用度。方法 20只食蟹猴皮下或静脉给予1,3或10mg·kg-1抗TNF-α全人源单抗,用ELISA试剂盒测定食蟹猴血浆中抗TNF-α全人源单抗的含量,研究其给药后168 h内药代动力学特征与生物利用度。结果抗TNF-α全人源单抗皮下注射给药的低中高3个剂量分别为1,3,10mg·kg-1时,AUC0-168随着剂量的增大而增大(P<0.05),而t1/2、Vz/F、Cl/F均不随剂量而改变(P>0.05)。比较中剂量的皮下与静脉2种给药方式,结果抗TNF-α全人源单抗皮下给药的生物利用度为77.5%。结论在本实验的给药浓度范围内,且在给药后168 h内,抗TNF-α全人源单抗在食蟹猴血浆中的暴露呈线性药代动力学特征,且皮下给药生物利用度较高,体内吸收良好。
Objective To study the pharmacokinetics and bioavailability of anti-tumor necrosis factor-α (TNF-α) human monoclonal antibodies in cynomolgus monkeys. Methods 20 cynomolgus monkeys were injected subcutaneously or intravenously with 1, 3 or 10 mg · kg -1 anti-TNF-α full-human monoclonal antibody. The content of anti-TNF-α whole human monoclonal antibody in plasma of cynomolgus monkeys , To study its pharmacokinetic characteristics and bioavailability within 168 h after administration. Results After 3, 10 and 10 mg · kg-1 doses of subcutaneous injection of anti-TNF-α allogeneic human monoclonal antibody were administered subcutaneously, AUC0-168 increased with increasing dose (P <0.05) , While t1 / 2, Vz / F, Cl / F did not change with dose (P> 0.05). Compared with the 2 doses of subcutaneous and intravenous modes of administration, the bioavailability of anti-TNF-α whole-body mAb administered subcutaneously was 77.5%. Conclusions The exposure of anti-TNF-α full-human mAbs to cynomolgus monkey plasma exhibits linear pharmacokinetic characteristics within the experimental concentration range and within 168 h after administration, and subcutaneous administration of biological High utilization, good absorption in the body.