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Objective: through production on the North China Pharmaceutical Group New Drug Research and Development Co., Ltd. HuMabs (NM57) in vivo pharmacokinetic studies in rats and monkeys, the pharmacokinetic characteristics of HuMabs (NM57) to provide objective and accurate evaluation, in order to the design and optimization of clinical research administration program provides a strong theoretical basis. Method: the radioisotope 125 I mark combined the TCA precipitation gel high-performance liquid chromatography (SHPLC) absorption study in rats, HuMabs (NM57), distribution, metabolism and excretion process. Indirect ELISA macaque serum samples HuMabs (NM57) concentration, and the body's metabolic processes in the macaque HuMabs (NM57). Results and conclusions: macaque i. m20 IU · mL -1 60 IU · mL -1 and 120 IU · mL -1 HuMabs (NM57), slower absorption serum drug concentrations were 92.0 ± 54.1 h, 84.0 ± 43.3 h, peak, peak concentration of 80.0 ± 27.7 h were 217.6 ± 67.2 ng · mL -1 , 812.4 ± 124.6 ng · mL < sup> -1 and 1783.8 ± 356.7ng · mL -1 , and then began a slow process of elimination, the three dose groups, serum drug concentrations can be detected to 552 h to 552 h basically down to the bottom. Low, medium and high dose groups dose ratio of 1:3:6, the drug peak concentration ratio of 1:3.7:8.2, AUC (0-552h) ratio of 1:5.0 : 9.7, basic dose positively correlated, suggesting linear pharmacokinetic properties of the drug. Some point in time between the middle and high dose groups serum drug concentration difference was statistically significant. Macaque i. v20 IU · mL -1 HuMabs (NM57) after 5 min plasma concentration of 822.9 ± 115.9 ng · mL -1 , and then gradually decreased to 552 h basic drop to the background level. And i. m dose HuMabs (NM57) compared to i 120 h. v blood concentration than i. m, 120 h after i. m above i. v, 408 h after tend to be similar. i. V and i. The m group the same point in time paired t-test a few time points the difference was statistically significant. Macaque i. the m20 IU · mL the -1 HuMabs (NM57) absolute bioavailability was 72.6% ± 33.7%, but the macaques between individuals quite different. Macaque i. The m 20 IU · mL -1 HuMabs (NM57) 0,3,7,14 days i. m rabies vaccine, separate macaque i. m 20 IU · kg -1 HuMabs (NM57) group, paired t-test to the same point in time, 240h before the difference is not statistically significant, 240h difference was statistically significant after intramuscular injection of rabies vaccine group The surge of anti-rabies virus antibody after 408h, in line with the principle of the role of the rabies virus vaccine. SD rats i. m 125 after the I-HuMabs (NM57), slower absorption peak time T max average total radioactivity and acid precipitation radioactive peak concentrations were 44.0 ± 14.5 h; 498.2 ± 36.9 ng · mL -1 and 493.6 ± 37.2ng · mL -1 ; the the AUC -432h were 77.6 ± 16.9μg · h · mL -1 and 75.6 ± 16.8μg · h · mL -1 ; MRT were 102.7 ± 18.2h and 100.5 ± 18.4 h; clearance CL 1.3 ± 0.2 mL · h -1 · kg -1 and 1.3 ± 0.2 mL · h -1 · kg -1 ; V ss were 130.7 ± 6.3 mL · kg -1 and 132.2 ± 6.4 mL · kg -1 ; terminal elimination half-life phase T 1/2 were 115.0 ± 35.1 h and 98.6 ± 30.0 h. Total radioactivity and radioactivity of TCA precipitation absolute bioavailability were 81.3 ± 4.4% and 79.2 ± 8.3%, relatively high bioavailability. HuMabs (NM57) is widely distributed in mice, no clear targeting excretion through urine excretion. The plasma protein binding of the drug tests showed 125 I-HuMabs (NM57) with rat plasma protein binding.
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