Pharmacokinetics,Biodistribution and Elimination of Recombinant Human Homoserine Thymosin α1 in Rats and Mice

Objective: To study the pharmacokinetic, distribution and elimination properties of rhTα 1 after intravenous(i.v.) and subcutaneous(s.c.)injection in mice and rats. Methods: Competition ELISA was used for testing drug concentration in serum, urine, bile and tissue after administration of rhTα 1 in mice(0.16, 0.5, 2.5 mg/kg) and rats(0.32, 1, 5 mg/kg). Pharmacokinetic parameters were calculated by Win Nolin software. Results: Absorption of rh Tαl is rapid in both mice and rats after s.c. administration. The pharmacokinetics in mice are characterized by linear, T_(1/2) showed a prolongation with increasing dose, 1.10, 1.35, and 1.50 h corresponding to 0.32, 1 and 5 mg/kg respectively, but in rats T_(1/2) showed no difference among doses. AUC0-∞ showed a clear increase with increasing doses in mice(904.18, 2998.83, and 19001.82 h*ng/m L) and in rats(1327.56 ±237.00,2924.53 ±685.14, and 35286.26 ±5999.58 h*ng/m L). After i.v. administration of 1 mg/kg rhTα 1 in mice, the drug is seen distributed in most organs, the thymus/serum exposure ratio was higher than others at the 1 and 2 h, the accumulative urinary excretion of primary drug was 32.97% ±15.85% within 6 h. Conclusion: The results indicate that rapid absorption, extensive distribution and quick renal excretion were the basic kinetic characteristics of rh Tαl after s.c. and i.v. administration.