BAYESIAN PHARMACOKINETIC ESTIMATION OF VINORELBINE IN NON-SMALL-CELL LUNG-CANCER PATIENTS

Objective: To develop a population pharmacokinetics of vinorelbine in a population of non-small-cell lung cancer (NSCLC) patients using a Ba yesian estimation in order to calculate for any further patient. indiv idual pharmacokinetic parameters from few blood samples. Methods: Vino relbine was given by a 15-min infusion (30 mg.m(-1)) to eight patients with NSCLC. Its serum concentration was determined by HPLC and its ph armacokinetics was described by a three-compartment open model with el imination from the central compartment. Volume of the central compartm ent (V-1) and rate constants (k(10), k(12), k(21), k(13), k(31)) were selected as population pharmacokinetic parameters and computed by non- linear regression (two-step approach) from 14 to 18 concentration meas urements per course. Subsequently, these parameters were used by the B ayesian estimator to calculate individual pharmacokinetics from only 2 or 3 measured concentrations. Results: The population mean values (CV %) of V-1, k(10), k(12), k(21), k(13), k(31), CL, t(1/2 gamma) were re spectively 21 1(55%). 3.2 h(-1) (29%), 7.7 h(-1) (74%), 1.3 h(-1) (67% ), 4.7 h(-1) (53%). 0.04 h(-1) (20%), 57 1.h(-1) (31%) and 43 h (36%). The comparison of results obtained from the Bayesian estimator and fr om the three-compartment model showed that CL and t(1/2 gamma) were we ll predicted (relative deviation: +/- 12 to 22%) by the Bayesian metho d using only two blood samples. Conclusion: We demonstrated that Bayes ian estimation allows, at minimal cost and minimal disturbance for the patient, the determination of several vinorelbine pharmacokinetic par ameters and therefore dose adaptation from as few as two drug concentr ations, measured at 6 h and 24 h after infusion.