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

Authors : Merve KURTAN YÜKSEL, Dilek ÖZTÜRK, Ezgi ÖZTAŞ, Gül ÖZHAN, Aylin ALTANLAR TÜRKER, Taner KORKMAZ, Alper OKYAR, Zeliha PALA KARA

Pages : 64-69

View : 37 | Download : 11

Publication Date : 2019-08-01

Article Type : Research Paper

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 insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(rs8192950); was genotyped using the reverse transcription-polymerase chain reaction. Patients were found to have heterozygote insert ignore into journalissuearticles values(57%);, wild insert ignore into journalissuearticles values(29%);, and mutant insert ignore into journalissuearticles values(14%); distributions of genotypes insert ignore into journalissuearticles values(p=0.909);. The mean plasma area under the curve insert ignore into journalissuearticles values(AUC0-4h); was 4.60±2.25 µg.h/mL, and maximum plasma concentration insert ignore into journalissuearticles values(Cmax); was 3.19±2.5 µg/mL. There were no statistically significant differences between genotypes and AUC values insert ignore into journalissuearticles values(p=0.2236); and the most frequently observed side effects were diarrhea insert ignore into journalissuearticles values(p=0.1028);, asthenia insert ignore into journalissuearticles values(p=0.6456);, anemia insert ignore into journalissuearticles values(p=0.6456);, emesis insert ignore into journalissuearticles values(p=0.3499);. This is the first study evaluating an association of genetic variation in CES1 insert ignore into journalissuearticles values(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 insert ignore into journalissuearticles values(2019);. Evaluation of the association of SNP in carboxylesterase enzyme insert ignore into journalissuearticles values(CES1); with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients. Istanbul J Pharm 49 insert ignore into journalissuearticles values(2);: 64-69.
Keywords : Capecitabine, carboxylesterase, pharmacogenetics, breast cancer, colorectal cancer

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