Patients carrying CYP2C83 have shorter systemic paclitaxel exposure

• Published in: Pharmacogenomics Vol. 20; no. 2; pp. 95 - 104
• Main Authors: Marcath, Lauren A, Kidwell, Kelley M, Robinson, Adam C, Vangipuram, Kiran, Burness, Monika L, Griggs, Jennifer J, Poznak, Catherine Van, Schott, Anne F, Hayes, Daniel F, Henry, Norah Lynn, Hertz, Daniel L
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.01.2019
• Subjects: Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Breast cancer; Consortia; Cytochrome P-450 CYP2C8 - genetics; Drug dosages; Family medical history; Female; Genetic Association Studies; Genomics; Genotype; Genotype & phenotype; Genotypes; Humans; Liver-Specific Organic Anion Transporter 1 - genetics; Male; Metabolism; Middle Aged; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Patients; Pharmacogenomic Variants - genetics; Phenotype; Phenotypes; Plasma; Polymorphism; Software; Tumors; United States > US; paclitaxel; pharmacogenomics
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs-2018-0162

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 ]). Second, screen additional pharmacogenes for associations with T . Methods: Pharmacogene panel genotypes were translated into genetic phenotypes for associations with T (n = 58). Patients with predicted low-activity CYP2C8 had shorter T 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 (12.12 vs 10.15 hrs, β = 0.85, p = 0.012). Contrary to previous publications, CYP2C8*3 may confer increased paclitaxel metabolic activity. SLCO1B1 and CYP2C8 genotype may explain some paclitaxel pharmacokinetic variability.