Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.

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  • Additional Information
    • Source:
      Publisher: Future Medicine Ltd Country of Publication: England NLM ID: 100897350 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1744-8042 (Electronic) Linking ISSN: 14622416 NLM ISO Abbreviation: Pharmacogenomics Subsets: MEDLINE
    • Publication Information:
      Publication: London : Future Medicine Ltd
      Original Publication: London : Ashley Publications,
    • Subject Terms:
      Cytochrome P-450 CYP2C8/*genetics ; Liver-Specific Organic Anion Transporter 1/*genetics ; Neoplasms/*drug therapy ; Paclitaxel/*adverse effects; Antineoplastic Agents, Phytogenic/administration & dosage ; Antineoplastic Agents, Phytogenic/adverse effects ; Female ; Genetic Association Studies ; Genotype ; Humans ; Male ; Middle Aged ; Neoplasms/genetics ; Neoplasms/pathology ; Paclitaxel/administration & dosage ; Pharmacogenomic Variants/genetics ; Phenotype
    • Abstract:
      Aim: First, evaluate if patients carrying putatively diminished activity CYP2C8 genotype have longer paclitaxel exposure (e.g., time above threshold concentration of 0.05 μM [T c >0.05 ]). Second, screen additional pharmacogenes for associations with T c >0.05 . Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with T c >0.05 (n = 58).
      Results: Patients with predicted low-activity CYP2C8 had shorter T c >0.05 after adjustment for age, body surface area and race (9.65 vs 11.03 hrs, β = 5.47, p = 0.02). This association was attributed to CYP2C8*3 (p = 0.006), not CYP2C8*4 (p = 0.58). Patients with predicted low-activity SLCO1B1 had longer T c >0.05 (12.12 vs 10.15 hrs, β = 0.85, p = 0.012).
      Conclusion: Contrary to previous publications, CYP2C8*3 may confer increased paclitaxel metabolic activity. SLCO1B1 and CYP2C8 genotype may explain some paclitaxel pharmacokinetic variability.
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    • Grant Information:
      UL1 TR000433 United States TR NCATS NIH HHS; KL2 TR002241 United States TR NCATS NIH HHS; P30 CA046592 United States CA NCI NIH HHS; KL2 TR000434 United States TR NCATS NIH HHS; UL1 TR002240 United States TR NCATS NIH HHS
    • Contributed Indexing:
      Keywords: ; paclitaxel; pharmacogenomics
    • Accession Number:
      0 (Antineoplastic Agents, Phytogenic)
      0 (Liver-Specific Organic Anion Transporter 1)
      0 (SLCO1B1 protein, human)
      EC 1.14.14.1 (CYP2C8 protein, human)
      EC 1.14.14.1 (Cytochrome P-450 CYP2C8)
      P88XT4IS4D (Paclitaxel)
    • Publication Date:
      Date Created: 20181207 Date Completed: 20200226 Latest Revision: 20200309
    • Publication Date:
      20240829
    • Accession Number:
      PMC6562943
    • Accession Number:
      10.2217/pgs-2018-0162
    • Accession Number:
      30520341