Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients

Year 2019, Volume: 49 Issue: 2, 64 - 69, 01.08.2019

Merve Kurtan Yüksel Dilek Öztürk Ezgi Öztaş Gül Özhan Aylin Altanlar Türker Taner Korkmaz Alper Okyar Zeliha Pala Kara

Abstract

DOI: 10.26650/IstanbulJPharm.2019.19018

Capecitabine is an oral prodrug and
converted to 5-fluorouracil using three-step enzymatic pathways which include
carboxylesterase (CES).  Interindividual
differences in the activities of drug-metabolizing enzymes may affect efficacy
and toxicity. The aim of this study is to evaluate the association of Single
nucleotide polymorphisms (SNP) in CES1 with the pharmacokinetic and adverse
effects of capecitabine. Plasma samples were obtained from 7 breast and
colorectal cancer patients who were treated with capecitabine-based
chemotherapy (1000-1250 mg/m2) at 0.5, 1, 2, 3 and 4 hours following drug
administration on their first day of the first cycle. The plasma concentrations
of the capecitabine were determined by using a high-pressure liquid
chromatography-UV detector. SNP (rs8192950) was genotyped using the reverse
transcription-polymerase chain reaction. Patients were found to have
heterozygote (57%), wild (29%), and mutant (14%) distributions of genotypes
(p=0.909). The mean plasma area under the curve (AUC0-4h) was 4.60±2.25
µg.h/mL, and maximum plasma concentration (Cmax) was 3.19±2.5 µg/mL. There were
no statistically significant differences between genotypes and AUC values
(p=0.2236) and the most frequently observed side effects were diarrhea
(p=0.1028), asthenia (p=0.6456), anemia (p=0.6456), emesis (p=0.3499). This is
the first study evaluating an association of genetic variation in CES1
(rs8192950) with pharmacokinetic and adverse effects of capecitabine.
Therefore, additional study in larger groups of patients is required to support
our study. 

Cite this article as: Kurtan Yüksel M,
Öztürk D, Öztaş E, Özhan G, Altanlar Türker A, Korkmaz T, Okyar A, Pala Kara Z
(2019). Evaluation of the association of SNP in carboxylesterase enzyme (CES1)
with pharmacokinetic and adverse effects of capecitabine in breast and
colorectal cancer patients. Istanbul J Pharm 49 (2): 64-69.

Keywords

Capecitabine, carboxylesterase, pharmacogenetics, breast cancer, colorectal cancer

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