A Limited Sampling Model with Bayesian Estimation to Determine Inulin Pharmacokinetics Using the Population Data Modelling Program P-PHARM

Abstract

This study describes the methodology used to calculate the individual clearance (CL) and volume of distribution (Vd) of inulin using 1 or 2 blood samples taken during the disposition and elimination phase after a single intravenous perfusion, and the population parameters. The mean population parameters and their interindividual variability were obtained from an initial group of 90 patients including 38.5% who had diabetes, 49% who were obese, and 12.5% who were diabetic and obese. Among these patients, 44.5% had normal renal function (creatinine clearance ranging from 70 to 150 ml/min/1.73m2) and 20% showed renal insufficiency with a creatinine clearance ranging from 15 to 60 ml/min/1.73m2. A 2-compartment model was fitted to the population data using P-PHARM. The population parameter estimates of CL and Vd were 6.85 ± 1.04 L/h and 4.95 ± 0.84L, respectively. The interindividual variability of CL was explained by a linear dependency between serum creatinine and body area. The interindividual variability of Vd was explained by a linear dependency with body area. A test group of 25 additional patients was used to evaluate the predictive performance of the population parameters. Seven blood samples were collected from each individual in order to calculate individual parameter estimates using standard fitting procedures. These values were compared with those estimated by means of a Bayesian approach using population parameters and 1 or 2 samples selected from the individual observations. The results show that the bias of CL and Vd, estimated using either 1 or 2 samples, was not statistically different from zero, and that the precision of these parameters was excellent.