Pharmacogenomics | 2019
Patients carrying CYP2C8*3 have shorter systemic paclitaxel exposure.
Abstract
AIM\n\xa0First, evaluate if patients carrying putatively diminished activity CYP2C8 genotype have longer paclitaxel exposure (e.g., time above threshold concentration of 0.05\xa0μM [Tc >0.05]). Second, screen additional pharmacogenes for associations with Tc >0.05.\xa0Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with Tc >0.05 (n\xa0=\xa058).\n\n\nRESULTS\nPatients 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\xa0=\xa05.47, p\xa0=\xa00.02). This association was attributed to CYP2C8*3 (p\xa0=\xa00.006), not CYP2C8*4 (p\xa0=\xa00.58). Patients with predicted low-activity SLCO1B1 had longer Tc >0.05 (12.12 vs 10.15\xa0hrs, β\xa0=\xa00.85, p\xa0=\xa00.012).\n\n\nCONCLUSION\nContrary to previous publications, CYP2C8*3 may confer increased paclitaxel metabolic activity. SLCO1B1 and CYP2C8 genotype may explain some paclitaxel pharmacokinetic variability.