A simultaneous oral/intravenous population pharmacokinetic model for vinorelbine.

摘要: Abstract Objectives. To develop a population pharmacokinetic (PK) model for simultaneous analysis of oral and intravenous data, to compare the variability between two routes administration vinorelbine, search main patient characteristics that explain this variability, estimate mean bioavailability vinorelbine. Patients methods. A PK was developed from 175 phase I/II patients (419 courses) treated by (20–45 mg/m2) and/or (60–100 mg/m2) vinorelbine given as monotherapy. Oral data were simultaneously fitted using NONMEM program, allowing estimation parameters such factor in who received only formulation. Covariates included demographic characteristics, biological markers, hematological parameters, liver metastases, early vomiting, food intake. The covariate rich sampling (n=187 I then assessed sparse (n=232 II courses). Results. three-compartment best described combined oral/intravenous blood concentration-time data. absolute 36%, with moderate interindividual (CV=20%) intraindividual (CV=19%) variability. Bayesian clearance accurately estimated 180 187 patients. showed comparable at usual doses (25–30 mg/m2 intravenous; CV=26%; 60–80 mg/m2 oral, CV=33%) moderately increased when including maximum tolerated (20–45 mg/m2 intravenous, CV=27%; 60-100 mg/m2 CV=36%). Several relevant relationships influencing total body independent route administration: surface area (proportional relationship), platelet count above 400×109/l (negative correlation), creatinine (positive elevated transaminases correlation). Food intake induced lag time absorption weak poorly relationship observed alkaline phosphatase levels bioavailability, although hepatic markers GGT, LDH, protein, metastases age had no effect on pharmacokinetics. Conclusions. By means (F=36%) its associated estimated. At similar routes. As result identification covariates their confirmation further explorations based limited strategies are now possible. use allows better characterization profile after either vascular or