Patients Carrying CYP2C8*3have Shorter Systemic Paclitaxel Exposure

Aim: First, evaluate if patients carrying putatively diminished activity CYP2C8genotype 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 >0.05after 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*3may confer increased paclitaxel metabolic activity. SLCO1B1and CYP2C8genotype may explain some paclitaxel pharmacokinetic variability.