Clinical pharmacokinetics of capecitabine and its metabolites in colorectal cancer patients.

Background: Capecitabine is one of the fluoropyrimidine anticancer agents which is extensively used in the management of colorectal cancer. We have noticed a discrepancy between the doses we are using in our patients and the recommended dosing regimen. Thus, this study aims to assess the pharmacokinetic parameters of capecitabine and its metabolites in colorectal cancer patients and report some clinical outcomes.

Methods: This study is a prospective observational pharmacokinetic study. It was conducted at the Oncology Center at King Saud University Medical City. The study included adult patients who received capecitabine for any stage of colorectal cancer. Blood samples were collected following the oral administration of capecitabine. Capecitabine and its metabolites concentration in plasma were determined using HPLC and pharmacokinetic parameters were estimated using PKanalix software.

Results: The study included 30 colorectal cancer patients with a mean age of 58 ± 9.5 years and ECOG Performance Status of 0-1. 60 % of the patients were in stage IV. The average total daily dose was 1265 ± 350 mg/m/day. C for capecitabine was 5.2 ± 1.3 μg/ mL and T was 1 ± 0.25 h. AUC for capecitabine was 28 ± 10 μg.h/ mL. Vd and Cl for capecitabine were 186 ± 28 L and 775 ± 213 mL/min, respectively. Calculated half-life (t) was 2.7 h. Half of our patients showed partial tumor response and 20% showed stable disease. Only two patients had to discontinue the treatment because of the toxicity.

Conclusion: Despite using lower doses, capecitabine and its metabolites parameters were found to be similar to previous studies except for the longer half-life found in our patients. In addition, lower doses of capecitabine showed acceptable response rate which might indicate that higher doses are not always necessary to achieve desired therapeutic effect.