İstanbul Journal of Pharmacy

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Research Article


DOI :10.26650/IstanbulJPharm.2019.19018   IUP :10.26650/IstanbulJPharm.2019.19018    Full Text (PDF)

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

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

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. 

Keywords: Capecitabine, carboxylesterase, pharmacogenetics, breast cancer, colorectal cancer

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APA

Pala Kara, Z., Kurtan Yüksel, M., Öztürk, D., Öztaş, E., Özhan, G., Altanlar Türker, A., Korkmaz, T., & Okyar, A. (0001). Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients. İstanbul Journal of Pharmacy, 49(2), 64-69. https://doi.org/10.26650/IstanbulJPharm.2019.19018


AMA

Pala Kara Z, Kurtan Yüksel M, Öztürk D, Öztaş E, Özhan G, Altanlar Türker A, Korkmaz T, Okyar A. Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients. İstanbul Journal of Pharmacy. 0001;49(2):64-69. https://doi.org/10.26650/IstanbulJPharm.2019.19018


ABNT

Pala Kara, Z.; Kurtan Yüksel, M.; Öztürk, D.; Öztaş, E.; Özhan, G.; Altanlar Türker, A.; Korkmaz, T.; Okyar, A. Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients. İstanbul Journal of Pharmacy, [Publisher Location], v. 49, n. 2, p. 64-69, 0001.


Chicago: Author-Date Style

Pala Kara, Zeliha, and Merve Kurtan Yüksel and Dilek Öztürk and Ezgi Öztaş and Gül Özhan and Aylin Altanlar Türker and Taner Korkmaz and Alper Okyar. 0001. “Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients.” İstanbul Journal of Pharmacy 49, no. 2: 64-69. https://doi.org/10.26650/IstanbulJPharm.2019.19018


Chicago: Humanities Style

Pala Kara, Zeliha, and Merve Kurtan Yüksel and Dilek Öztürk and Ezgi Öztaş and Gül Özhan and Aylin Altanlar Türker and Taner Korkmaz and Alper Okyar. “Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients.” İstanbul Journal of Pharmacy 49, no. 2 (Nov. 2024): 64-69. https://doi.org/10.26650/IstanbulJPharm.2019.19018


Harvard: Australian Style

Pala Kara, Z & Kurtan Yüksel, M & Öztürk, D & Öztaş, E & Özhan, G & Altanlar Türker, A & Korkmaz, T & Okyar, A 0001, 'Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients', İstanbul Journal of Pharmacy, vol. 49, no. 2, pp. 64-69, viewed 25 Nov. 2024, https://doi.org/10.26650/IstanbulJPharm.2019.19018


Harvard: Author-Date Style

Pala Kara, Z. and Kurtan Yüksel, M. and Öztürk, D. and Öztaş, E. and Özhan, G. and Altanlar Türker, A. and Korkmaz, T. and Okyar, A. (0001) ‘Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients’, İstanbul Journal of Pharmacy, 49(2), pp. 64-69. https://doi.org/10.26650/IstanbulJPharm.2019.19018 (25 Nov. 2024).


MLA

Pala Kara, Zeliha, and Merve Kurtan Yüksel and Dilek Öztürk and Ezgi Öztaş and Gül Özhan and Aylin Altanlar Türker and Taner Korkmaz and Alper Okyar. “Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients.” İstanbul Journal of Pharmacy, vol. 49, no. 2, 0001, pp. 64-69. [Database Container], https://doi.org/10.26650/IstanbulJPharm.2019.19018


Vancouver

Pala Kara Z, Kurtan Yüksel M, Öztürk D, Öztaş E, Özhan G, Altanlar Türker A, Korkmaz T, Okyar A. Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients. İstanbul Journal of Pharmacy [Internet]. 25 Nov. 2024 [cited 25 Nov. 2024];49(2):64-69. Available from: https://doi.org/10.26650/IstanbulJPharm.2019.19018 doi: 10.26650/IstanbulJPharm.2019.19018


ISNAD

Pala Kara, Zeliha - Kurtan Yüksel, Merve - Öztürk, Dilek - Öztaş, Ezgi - Özhan, Gül - Altanlar Türker, Aylin - Korkmaz, Taner - Okyar, Alper. “Evaluation of the association of SNP in carboxylesterase enzyme (CES1) with pharmacokinetic and adverse effects of capecitabine in breast and colorectal cancer patients”. İstanbul Journal of Pharmacy 49/2 (Nov. 2024): 64-69. https://doi.org/10.26650/IstanbulJPharm.2019.19018



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Accepted17.07.2019

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