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Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer
University of South Denmark.
University of South Denmark.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Odense University Hospital.
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2011 (English)In: PHARMACOGENOMICS JOURNAL, ISSN 1470-269X, Vol. 11, no 2, 113-120 p.Article in journal (Refereed) Published
Abstract [en]

The primary purpose of this study was to evaluate the effect of CYP2C8*3 and three genetic ABCB1 variants on the elimination of paclitaxel. We studied 93 Caucasian women with ovarian cancer treated with paclitaxel and carboplatin. Using sparse sampling and nonlinear mixed effects modeling, the individual clearance of unbound paclitaxel was estimated from total plasma paclitaxel and Cremophor EL. The geometric mean of clearance was 385 l h(-1) (range 176-726 l h(-1)). Carriers of CYP2C8*3 had 11% lower clearance than non-carriers, P = 0.03. This has not been shown before in similar studies; the explanation is probably the advantage of using both unbound paclitaxel clearance and a population of patients of same gender. No significant association was found for the ABCB1 variants C1236T, G2677T/A and C3435T. Secondarily, other candidate single-nucleotide polymorphisms were explored with possible associations found for CYP2C8*4 (P = 0.04) and ABCC1 g.7356253C andgt; G (P = 0.04).

Place, publisher, year, edition, pages
Nature Publishing Group , 2011. Vol. 11, no 2, 113-120 p.
Keyword [en]
CYP2C8, ABCB1, P-glycoprotein, paclitaxel, cremophor, ovarian cancer
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-67364DOI: 10.1038/tpj.2010.19ISI: 000288849900005OAI: oai:DiVA.org:liu-67364DiVA: diva2:409710
Note
Original Publication: T K Bergmann, C Brasch-Andersen, Henrik Green, M Mirza, R S Pedersen, F Nielsen, K Skougaard, J Wihl, N Keldsen, P Damkier, L E Friberg, Curt Peterson, W Vach, M O Karlsson and K Brosen, Impact of CYP2C8*3 on paclitaxel clearance: a population pharmacokinetic and pharmacogenomic study in 93 patients with ovarian cancer, 2011, PHARMACOGENOMICS JOURNAL, (11), 2, 113-120. http://dx.doi.org/10.1038/tpj.2010.19 Copyright: Nature Publishing Group http://npg.nature.com/ Available from: 2011-04-11 Created: 2011-04-11 Last updated: 2011-09-06

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