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Dexamethasone as a probe for vinorelbine clearance
Author(s) -
Puisset Florent,
Dalenc Florence,
Chatelut Etienne,
Cresteil Thierry,
Lochon Isabelle,
Tisnes Pierre,
Roché Henri
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02384.x
Subject(s) - vinorelbine , dexamethasone , pharmacokinetics , population , nonmem , pharmacology , medicine , volume of distribution , endocrinology , chemotherapy , environmental health , cisplatin
Aim To assess the value of using dexamethasone as an in vivo probe for predicting vinorelbine clearance (CL). Methods A population approach (implemented with NONMEM) was used to analyse blood vinorelbine pharmacokinetic data from 20 patients who received a 20‐min intravenous infusion of vinorelbine (from 20 to 30 mg m −2 ). Selected patient clinical data as well as known functional single CYP3A5 and ABCB1 genotype were also tested as covariates. Results The best covariate model (with ± 95% confidence intervals) was based on dexamethasone plasma clearance (DPC) and alkaline phosphatase (ALP): vinorelbine blood CL (l h −1 ) = 39.8(± 4.0) × (DPC/13.2) 0.524(±0.322) × (ALP/137) −0.198(±0.158) . Interindividual variability in vinorelbine CL decreased from 29.7% (model without covariate) to 14.7% when including DPC and ALP. Vinorelbine CL was not correlated with body surface area (BSA) or associated with CYP3A5 and ABCB1 genotype. Conclusions These results indicate that individualization of vinorelbine dose would be improved by using dexamethasone clearance rather than BSA. Dexamethasone merits further evaluation as a probe of CYP3A metabolism.