A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine.

Objectives: To develop a population pharmacokinetic (PK) model for simultaneous analysis of oral and intravenous data, to compare the variability between the two routes of administration of vinorelbine, to search for the main patient characteristics that explain this variability, and to estimate the mean population bioavailability of oral vinorelbine.

Patients And Methods: A PK model was developed from 175 phase I/II patients (419 courses) treated by intravenous (20-45 mg/m2) and/or oral (60-100 mg/m2) vinorelbine given as monotherapy. Oral and intravenous PK data were simultaneously fitted using the NONMEM program, allowing the estimation of oral PK parameters such as the bioavailability factor in patients who received only the oral formulation.

The effects of food on the pharmacokinetic profile of oral vinorelbine.

The effects of food on the pharmacokinetics and safety profile of a soft-gel capsule formulation of vinorelbine (Navelbine Oral) were evaluated in fed and fasted patients with solid tumours or lymphomas. A group of 18 patients (12 planned) were entered into a multicentre phase I pharmacokinetic study following a crossover design with a 1-week wash-out period. Patients received the first dose of 80 mg/m(2) oral vinorelbine either after fasting or after ingestion of a standard continental breakfast.

Population pharmacokinetics model and limited sampling strategy for intravenous vinorelbine derived from phase I clinical trials.

Aims: a) To characterize the pharmacokinetics of intravenous vinorelbine, b) to use a population analysis for the identification of patient covariates that might appreciably influence its disposition and c) to define a limited sampling strategy for further Bayesian estimation of individual pharmacokinetic parameters.

Methods: All data were collected from 64 patients (99 courses) entered in three different phase I trials that have been previously reported. All patients received vinorelbine as a 20 min infusion with dose levels ranging from 20-45 mg m-2.