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Research about the Possibility of Increasing the Bioavailability of Capecitabine

Stanila Stoeva, Iliyan Kolev, Yulichka Sabeva


Introduction: Capecitabine is an antimetabolite that belongs to the fluoropyrimidine carbamate class. It is a chemotherapy medication used to treat breast, gastric and colorectal cancer. Inside the organism, this pro-drug is converted to the active 5-fluorouracil (5-FU) that causes cell injury via RNA- and DNA-related mechanisms. The conversion is a three-step process with the participation of the enzymes - carboxylesterase (CES), cytidine deaminase and thymidine phosphorylase that are present in healthy and tumor cells. This research, specifically, is dedicated to CES isozymes CES1A1 and CES2, which convert Capecitabine to 5’-deoxy-5-fluorocytidine (5’-DFCR).

Materials and methods: To determine Capecitabine we have used: Thermo Scientific Dionex UltiMate 3000 Analytical LC System, VWD-3100 variable wavelength detector, Thermo Scientific™ Chromeleon™ 7.2 Chromatography Data System software. The chromatographic analysis was carried out by using a mobile phase of methanol: buffer (water with 1% formic acid) with a Thermo Scientific Accucore C18 (100 mm x 4.6 mm, 2.6μ) analytical column in gradient mode with UV detection at 310 nm.

Results: Recently, the structure of the active centre of isozymes CES1A1 and CES2 has been successfully determined. This allows the exploration of new or already known substances with structural similarity. It is important to investigate such supplements that could assist in the treatment without increasing the risk of adverse effects. A sensitive, accurate and reliable method for the determination of Capecitabine in pharmaceutical dosage forms and in human plasma was developed using a RP-HPLC. The established LOD and LOQ values allow us to conduct monitoring of the bioavailability of Capecitabine after CES-inhibitors application.

Conclusions: Based on the established relationship between structure and biological activity of known CES inhibitors new potential inhibitors with natural origin could be offered. Using the RP-HPLC allows us to research the pharmacokinetic parameters of Capecitabine after CES-inhibitors in further investigations.


Capecitabine, carboxylesterase, RP-HPLC


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