Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 100, Issue 10, Pages 4205-4209Publisher
WILEY-BLACKWELL
DOI: 10.1002/jps.22680
Keywords
CYP enzymes; pharmacogenetics; toxicity; polymorphism; drug metabolizing enzymes; cancer chemotherapy
Funding
- Swedish Cancer Society
- Swedish Research Council
- European Commission [CHEMORES LSHC-CT-2007-037665]
- Ostergotland County Council
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The influence of genetic variants on paclitaxel-induced toxicity is of considerable interest for reducing adverse drug reactions. Recently, the genetic variants CYP2C8(*)3, CYP2C8-HapC, and CYP3A5(*)3 were associated with paclitaxel-induced neurotoxicity. We, therefore, investigated the impact of CYP2C8-HapC and CYP3A5(*)3 on paclitaxel/carboplatin-induced myelosuppression and neurotoxicity. Thirty-three patients from a prospective pharmacokinetics study were genotyped using pyrosequencing. Patients with variant alleles of CYP2C8-HapC were found to have significantly lower nadir values of both leukocytes and neutrophils (p < 0.05) than patients with the wild-type genotype. CYP3A5(*)3/(*)1 patients were shown to have borderline, significantly lower nadir values of leukocytes (p = 0.07) than (*)3/(*)3 patients. Combining the two genotypes resulted in a significant correlation with both leukopenia and neutropenia (p = 0.01). No effect of these genetic variants on neurotoxicity could be shown in this rather small study, but their importance for paclitaxel-induced toxicity could be confirmed. (C) 2011Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 4205-4209, 2011
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