title: Dexamethasone as a probe for vinorelbine clearance.
abstract: OBJECTIVE
  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) 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.
  
  
  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.
authors.affiliation: EA3035, Institut Claudius-Regaud, Toulouse, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Puisset
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
authors.forename: Etienne
authors.initials: E
authors.lastname: Chatelut
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lochon
authors.forename: Pierre
authors.initials: P
authors.lastname: Tisnes
authors.forename: Henri
authors.initials: H
authors.lastname: Roché
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000097:blood / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D003907:Dexamethasone / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000077235:Vinorelbine
chemical_list: D018931:Antineoplastic Agents, Hormonal; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D000077235:Vinorelbine