PREDICTION OF BLOOD CYCLOSPORINE CONCENTRATIONS IN HEMATOLOGICAL PATIENTS WITH MULTIDRUG-RESISTANCE BY ONE-COMPARTMENT, 2-COMPARTMENT AND 3-COMPARTMENT MODELS USING BAYESIAN AND NONLINEAR LEAST-SQUARES METHODS

The blood cyclosporine (CsA) concentration-time profile in each of 24 adult haematological patients with multidrug resistance taking the fir st course of CsA treatment was fitted by one-, two- and three-compartm ent models to obtain relevant pharmacokinetic parameters, The pharmaco kinetic parameters obtained were implemented into the PKS program (Abb ottbase Pharmacokinetic System) as the population pharmacokinetic para meters used to predict blood CsA concentrations in adult haematologica l patients with multidrug resistance, The predictions of blood CsA con centrations by one-, two- and three-compartment models using the Bayes ian method (BM) and the non-linear least squares method (NLLSM) were e valuated employing 11 patients who took the second course of CsA treat ment. While the Akaike's information criterion (AIC) favoured the two- compartment model to describe CsA concentration-time profiles in patie nts taking the first and second courses of CsA treatment, the predicti ve performance analyses showed that both two- and three-compartment mo dels were better than the one-compartment model for prediction, but th e three-compartment model was slightly superior to the two-compartment model, The results also show that the predictions using BM were sligh tly better than those using NLLSM. Several factors affecting BM predic tions and the possible difference among AIC, BM and predictive perform ance analyses were also addressed. (C) 1996 The Italian Pharmacologica l Society