title: A limited-sampling strategy to estimate individual pharmacokinetic parameters of vinorelbine in elderly patients with advanced metastatic cancer.
abstract: The aim of this study was to characterize the population pharmacokinetic of vinorelbine in elderly patients and to propose a limited-sampling strategy to estimate individual pharmacokinetic parameters. Vinorelbine was administered by a 10-min continuous infusion at a dose of 20-30 mg/m2. The population parameters were computed, using a three-compartment model, from an initial group of 27 patients. Twelve additional courses were used for model validation and evaluation of eight different limited-sampling strategies. The inter-individual variability of CL was explained by a linear dependency with age. The population average parameters and the interindividual variabilities (CV%) were: CL=47.1 l/h (31.7%), V=16.6 l (64%), k21=0.776 h-1 (20%), k31=0.0346 h-1 (15.2%), alpha=0.431 h-1 (6.84%) and beta=0.0167 h-1 (25%). Bayesian estimation with three measured levels (end of infusion, and 6 and 48 h) can be selected, because it allows adequate estimation of CL, elimination half-life and vinorelbine concentrations with a non-significant bias. Moreover, the choice of these three sampling times presents practicality advantages for the patient's comfort. Vinorelbine clearance decreasing with age and AUC being a good predictor of several toxicity end points during vinorelbine treatment, the limited-sampling strategy developed in this paper may be clinically relevant.
authors.affiliation: Clinical Pharmacokinetic Laboratory, Faculty of Pharmacy, University Montpellier I, 34093 Montpellier, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Gauvin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pinguet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Culine
authors.forename: Cécile
authors.initials: C
authors.lastname: Astre
authors.forename: Roberto
authors.initials: R
authors.lastname: Gomeni
authors.forename: Françoise
authors.initials: F
authors.lastname: Bressolle
mesh_terms: D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001499:Bayes Theorem; D006801:Humans; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011153:Population; D012494:Sampling Studies; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine