A limited-sampling strategy to estimate individual pharmacokinetic parameters of vinorelbine in elderly patients with advanced metastatic cancer.
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.
Gauvin
Amélie
A
Clinical Pharmacokinetic Laboratory, Faculty of Pharmacy, University Montpellier I, 34093 Montpellier, France.
Pinguet
Frédéric
F
Culine
Stéphane
S
Astre
Cécile
C
Gomeni
Roberto
R
Bressolle
Françoise
F
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
D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D000077235:Vinorelbine