A pharmacokinetic model for alpha interferon administered subcutaneously

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Abstract
Aims To model the pharmacokinetic profiles of alpha interferon (αIFN) after a single subcutaneous (s.c.) injection of 3 million units of alpha 2b interferon, to correlate the pharmacokinetic parameters with patient demographic covariates, and to develop a limiting sampling strategy for determining the αIFN plasma area under the curve of concentration vs time (AUC). Methods The plasma αIFN pharmacokinetics were determined in 27 patients with chronic hepatitis C virus infection after the first s.c. injection of the drug. Ten patients had normal renal function and 17 were chronic haemodialysis patients. Plasma samples were assayed by an Elisa method. Concentration‐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 dialysis patients represented 37% (with 95% confidence interval: 30%–44%) of the mean value of the patients with normal renal function. The volume of distribution was significantly correlated to the body surface area. Bayesian analysis using NONMEM allowed determination of the individual plasma AUC from three samples within the 24 h period post s.c. injection. Conclusions The present pharmacokinetic model will allow one to obtain individual parameters such as, the area under the curve of concentration vs time from a limited‐sampling strategy, and to perform pharmacokinetic‐pharmacodynamic analysis of combined αIFN plasma concentrations and viraemic data.