Pharmacokinetics And Excretion Of Recombinant Human Ciliary Neurotrophic Factor In Rats

Aim To study the pharmacokinetics of Recombinant Human CiliaryNeurotrophic Factor (rhCNTF) and excretion from bile, urine and feces inrats, for the purpose of development of a new drug. Methods The concentrations of rhCNTF in samples were determinedby ELISA method. The pharmacokinetics parameters were calculated by3P87 software. Results (1)ELISA method was proved to be simple, sensitive, highlyspecific and precise, the recovery was respectively 85.6%(plasma),75.0%(bile),74.3%(urine)and 74.8%(feces). The linearity is all good during0.0625 ~ 2ng/ml. (2) After single iv dose of rhCNTF 300μg/kg to rats, theplasma concentration–time curve was fit to a two-compartment model andt1/2α was 7.5min, t1/2β was 73.2min, AUC was 32071.3ng/ml.min, CL(s) was0.0097L/kg/min. (3) After single sc doses of rhCNTF 100, 300, 1000μg/kg to rats, the plasma concentration-time curve was fit to aone-compartment model. Cmax and t1/2β were 9.2ng/ml and 92.4min at thelow dose of 100μg/kg, 27.3 ng/ml and 122.1min at the middle dose of 300μg/kg, 121.5ng/ml and 135.3min at the high dose of 1000μg/kgrespectively. Excepting AUC and Cmax, no significant differences wereobserved in the pharmacokinetics parameters among the three differentdoses. (4) after sc 300μg/kg in rats, the cumulative excretion in bile for 12hours was 0.002% and in urine for 24 hours was 0.026%. The drug wasn'tdetected in feces. Conclusion The elimination of rhCNTF in rats was of first orderkinetics and the speed of elimination was high. The bioavailability of scrhCNTF was low. And rhCNTF may mainly be metabolized.