Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab

Abstract

Aim: Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.

Patients and methods: Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study. In the first cycle CCB was given alone at doses of 1,250 mg/m2 bi-daily for two weeks with one week rest. In the second cycle BVZ co-administration started simultaneously with oral intake of CCB by short infusion of 7.5 mg/kg.

Results: Mean plasma concentration time curves of CCB and its metabolites were insignificantly lower in the BVZ combination regimen compared to CCB monotherapy. After repeated cycles of BVZ no significant pharmacokinetic interaction was observed.

Conclusion: From the pharmacokinetic point of view and in agreement with numerous clinical study data, co-administration of BVZ with CCB appears to be safe and efficient.

Keywords: Capecitabine; bevacizumab; colorectal cancer; drug-drug interaction; pharmacokinetics.