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Dexamethasone as a probe for vinorelbine clearance

Content Provider	Scilit
Author	Puisset, Florent Dalenc, Florence Chatelut, Etienne Cresteil, Thierry Lochon, Isabelle Tisnes, Pierre Roché, Henri
Copyright Year	2005
Description	Journal: British journal of clinical pharmacology To assess the value of using dexamethasone as an in vivo probe for predicting vinorelbine clearance (CL).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.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) x (DPC/13.2)(0.524(+/-0.322)) x (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.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.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1884916/pdf http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2005.02384.x/pdf
Ending Page	53
Page Count	9
Starting Page	45
e-ISSN	13652125
DOI	10.1111/j.1365-2125.2005.02384.x
Journal	British journal of clinical pharmacology
Issue Number	1
Volume Number	60
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2005-07-01
Access Restriction	Open
Subject Keyword	Journal: British journal of clinical pharmacology Medical Laboratory Technology Cytochrome P450 3a4/ 5 Population Pharmacokinetics
Content Type	Text
Resource Type	Article

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