摘要
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.
Objective:To study the pharmacokinetic,distribution and elimination properties of rhT α 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 rhT α 1 in mice (0.16,0.5,2.5 mg/kg) and rats (0.32,1,5 mg/kg).Pharmacokinetic parameters were calculated by WinNolin software.Results:Absorption of rhTα 1 is rapid in both mice and rats after s.c.administration.The pharmacokinetics in mice are characterized by linear,T1/2 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 Ti/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/rnL) and in rats (1327.56 ± 237.00,2924.53 ± 685.14,and 35286.26 ± 5999.58 h*ng/mL) After i.v.administration of 1 mg/kg rhTα1 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 3297％ ± 15.85％ within 6 h.Conclusion:The results indicate that rapid absorption,extensive distribution and quick renal excretion were the basic kinetic characteristics of rhTαl after s.c.and i.v.administration.
基金
Natural Science Foundation of Gansu Province
grant number:1506RJZA278
