Pharmacokinetics Of Recombinant Human Rabies Monoclonal Antibody

Aim: To study the pharmacokinetic property following single dosing of HuMabs(NM57) via the route of intramuimular injection in rhesus monkeys and mouse.Method:¹²⁵I-labelled HuMabs(NM57) which was prepared by Iodogen method was administered to BALB/C mouse and SD rats to study the ADME characteristics of HuMabs(NM57) by the method of tetrachloroacetic acid (TCA) precipitation and SHPLC. An indirect ELISA method was utilized to determined the level of HuMabs(NM57) in serum to research the PK profiles in rhesus monkeys. Result and Conclusion: Due to the relative slow absorption, the serum levels of ¹²⁵I-HuMabs(NM57) in rats increased slowly with a mean T_max of (44.0±14.5)h after im injection. The terminal T1/2 were (115.0±35.1)h and (98.6±30.0)h calculated by the radioactivity of total and TCA precipitable fraction, respectively. The absolute bioavailability was 81.3%±4.4% and 79.2%±8.3%, respectively. The distribution of HuMabs(NM57) were widely and slowly, and urine was the dominant way of excretion. In rhesus monkey, HuMabs(NM57) absorbed slowly with a T_max generally occurring 80-92h after im administration. Mean Cmax after im administration in three groups of 20IU·mL^-1, 60IU·mL^-1 and 120IU·mL^-1 were (217.6±67.2) ng·mL^-1, (812.4±124.6) ng·mL^-1, and (1783.8±35.6) ng·mL^-1, respectively, and then with a rather slow elimination process. The HuMabs(NM57) serum concentration were all declined to background concentration after 552h.Area under concentration-time curve increased linearly with dose, but systemic clearance were similar among different groups. The C_max following intravenous administration of 20IU·mL^-1 HuMabs(NM57) was (822.9±115.9) ng·mL^-1 with a T_max of 5min postdosing. The elimination was still slow similar to im administration. The absolute bioavailability was 72.6%±33.7% based on pooled data from 2QIU·mL^-1 with a rather big individual variability. A group of im administration of both HuMabs(NM57) and anti-rabies vaccine was designed to compare with that of single administered of 20TU·mL^-1 HuMabs(NM57).The anti-rabies vaccine was injected repeatedly on 0,3,7 and 14d after HuMabs(NM57) treated, and the level of antibody increased drastically 408h postdosing which was consistent with the known mechanism of anti-rabies vaccine.