E Chatelut, L Rostaing, N Grégoire, J-L Payen, A Pujol, J Izopet, G Houin, and P Canal
Institut Claudius-Regaud and Centre Hospitalier Universitaire, F-31052 Toulouse
Aims: To model the pharmacokinetic profiles of alpha 2b interferon (aIFN) after a single subcutaneous (s.c.) injection of 3 million units, to correlate the pharmacokinetic parameters with patients demographic covariates, and to develop a limiting sampling strategy for determining the aIFN plasma area under the curve of concentration versus time (AUC).
Patients and Methods: The plasma aIFN pharmacokinetics were determined in twenty seven patients with chronic hepatitis C virus infection after the first s.c. injection of the drug. Ten patients had a normal renal function and seventeen were chronic hemodialysis patients. Plasma samples were assessed by an Elisa test. Concentration-time data was analysed by population approach using NONMEM.
Results: The pharmacokinetic model which better described the concentration versus 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.
Conclusion: The present pharmacokinetic model will allow one to obtain individual parameters such as, the area under the curve of concentration versus time from a limited-sampling strategy, and to perform pharmacokinetic-pharmacodynamic analysis of combined aIFN plasma concentrations and viremic data.
Reference: PAGE 8 (1999) Abstr 142 [www.page-meeting.org/?abstract=142]
Poster: poster