The pharmacokinetics of cyclosporine. I. Single dose and constant rate infusion studies in the rabbit
Awni, W.M.; Sawchuk, R.J.
Drug Metabolism and Disposition the Biological Fate of Chemicals 13(2): 127-132
1985
ISSN/ISBN: 0090-9556 PMID: 2859157 Document Number: 247987
A 2-part study was conducted to characterize the pharmacokinetics of cyclosporine . The data indicate an increase in the half-life of the terminal phase (255-550 min), and in the volume of distribution at steady state (3.16-7.82 l/kg) with increasing dose (5-20 mg/kg). Cyclosporine was then administered to 3 rabbits by constant rate i.v. infusion. The infusion rate was altered to provide 3 different steady states within 36 h in each animal, infusion rates in 2 rabbits were increased from 16.8-65.4 .mu.g/min, and in the 3rd rabbit they were decreased from 65.4 to 16.8 .mu.g/min. Blood samples were collected during and postinfusion. Doubling the infusion rate within each animal produced less than double the steady state concentration. All 3 rabbits showed the same trend. The total body clearance of cyclosporine increased with increasing infusion rate, indicating nonlinear pharmacokinetic behavior of cyclosporine in rabbits.