A pharmacokinetic model for alpha interferon administered subcutaneously

Aims To model the pharmacokinetic profiles of alpha interferon (alpha IFN) after a single subcutaneous (s.c.) injection of 3 million units of alpha 2b interferon, to correlate the pharmacokinetic parameters with patient demog raphic covariates, and to develop a limiting sampling strategy for determin ing the alpha IFN plasma area under the curve of concentration vs time (AUC ). Methods The plasma alpha IFN pharmacokinetics were determined in 27 patient s with chronic hepatitis C virus infection after the first s.c. injection o f the drug. Ten patients had normal renal function and 17 were chronic haem odialysis patients. Plasma samples were assayed by an Elisa method. Concent ration-time data was analysed by a population approach using NONMEM. Results The pharmacokinetic model which better described the concentration vs time data was a one-compartment model with two processes of absorption: a zero-order followed by a first-order process. The mean clearance of dialy sis patients represented 37% (with 95% confidence interval: 30% -44%) of th e mean value of the patients with normal renal function. The volume of dist ribution was significantly correlated to the body surface area. Bayesian an alysis using NONMEM allowed determination of the individual plasma AUC h-om three samples within the 24 h period post s.c. injection. Conclusions The present pharmacokinetic model will allow one to obtain indi vidual parameters such as, the area under the curve of concentration vs tim e from a limited-sampling strategy, and to perform pharmacokinetic-pharmaco dynamic analysis of combined alpha IFN plasma concentrations and viraemic d ata.