Pharmacogenetic pathway analysis of docetaxel elimination

S. D. Baker, J. Verweij, G. A. Cusatis, R. H. Van Schaik, S. Marsh, S. J. Orwick, R. M. Franke, S. Hu, E. G. Schuetz, V. Lamba, W. A. Messersmith, Antonio C Wolff, Michael A Carducci, A. Sparreboom

Research output: Contribution to journalArticle

Abstract

The purpose of this study was to evaluate the affinity of docetaxel for 14 transporter proteins and assess the functional significance of 17 variants in five genes involved in drug elimination. Among the transfected models investigated, OATP1B3 (SLCO1B3) was identified as the most efficient influx transporter for docetaxel. None of the observed genotypes (SLCO1B3, ABCB1, and ABCC2) was related with docetaxel clearance in 92 white patients (P > 0.17). However, the simultaneous presence of the CYP3A4*1B and CYP3A5*1A alleles was associated with a 64% increase in docetaxel clearance (P <0.0015), independent of both sex and CYP3A activity (as determined using the erythromycin breath test). This haplotype was also associated with increased midazolam clearance in another population (P <0.0198). An analysis of the CYP3A locus among CEPH-HapMap samples revealed that CYP3A4*1B is present exclusively among a subset of CYP3A5 expressors. Therefore, future studies should first stratify the population on the basis of CYP3A5 genotype and then compare CYP3A activity between individuals with and without the CYP3A4*1B allele.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume85
Issue number2
DOIs
StatePublished - Feb 2009

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docetaxel
Cytochrome P-450 CYP3A
Alleles
Genotype
HapMap Project
Pharmacogenomic Testing
Breath Tests
Midazolam
Erythromycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Baker, S. D., Verweij, J., Cusatis, G. A., Van Schaik, R. H., Marsh, S., Orwick, S. J., ... Sparreboom, A. (2009). Pharmacogenetic pathway analysis of docetaxel elimination. Clinical Pharmacology and Therapeutics, 85(2), 155-163. https://doi.org/10.1038/clpt.2008.95

Pharmacogenetic pathway analysis of docetaxel elimination. / Baker, S. D.; Verweij, J.; Cusatis, G. A.; Van Schaik, R. H.; Marsh, S.; Orwick, S. J.; Franke, R. M.; Hu, S.; Schuetz, E. G.; Lamba, V.; Messersmith, W. A.; Wolff, Antonio C; Carducci, Michael A; Sparreboom, A.

In: Clinical Pharmacology and Therapeutics, Vol. 85, No. 2, 02.2009, p. 155-163.

Research output: Contribution to journalArticle

Baker, SD, Verweij, J, Cusatis, GA, Van Schaik, RH, Marsh, S, Orwick, SJ, Franke, RM, Hu, S, Schuetz, EG, Lamba, V, Messersmith, WA, Wolff, AC, Carducci, MA & Sparreboom, A 2009, 'Pharmacogenetic pathway analysis of docetaxel elimination', Clinical Pharmacology and Therapeutics, vol. 85, no. 2, pp. 155-163. https://doi.org/10.1038/clpt.2008.95
Baker SD, Verweij J, Cusatis GA, Van Schaik RH, Marsh S, Orwick SJ et al. Pharmacogenetic pathway analysis of docetaxel elimination. Clinical Pharmacology and Therapeutics. 2009 Feb;85(2):155-163. https://doi.org/10.1038/clpt.2008.95
Baker, S. D. ; Verweij, J. ; Cusatis, G. A. ; Van Schaik, R. H. ; Marsh, S. ; Orwick, S. J. ; Franke, R. M. ; Hu, S. ; Schuetz, E. G. ; Lamba, V. ; Messersmith, W. A. ; Wolff, Antonio C ; Carducci, Michael A ; Sparreboom, A. / Pharmacogenetic pathway analysis of docetaxel elimination. In: Clinical Pharmacology and Therapeutics. 2009 ; Vol. 85, No. 2. pp. 155-163.
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