Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.
Ontology highlight
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 [Tc >0.05]). Second, screen additional pharmacogenes for associations with Tc >0.05. Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with Tc >0.05 (n = 58).Results
Patients with predicted low-activity CYP2C8 had shorter Tc >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 Tc >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.
SUBMITTER: Marcath LA
PROVIDER: S-EPMC6562943 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.
Marcath Lauren A LA Kidwell Kelley M KM Robinson Adam C AC Vangipuram Kiran K Burness Monika L ML Griggs Jennifer J JJ Poznak Catherine Van CV Schott Anne F AF Hayes Daniel F DF Henry Norah Lynn NL Hertz Daniel L DL
Pharmacogenomics 20181206 2
<h4>Aim</h4>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<sub>c >0.05</sub>]). Second, screen additional pharmacogenes for associations with T<sub>c >0.05</sub>. Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with T<sub>c >0.05</sub> (n = 58).<h4>Results</h4>Patients with predicted low-activity CYP2C8 had shorter T<sub>c >0. ...[more]
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