Andre Farkouh1, Werner Scheithauer2, Philipp Buchner3, Apostolos Georgopoulos4, Johannes Schueller5, Birgit Gruenberger6, Martin Czejka3. 1. Division of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria andre.farkouh@univie.ac.at. 2. Department of Oncology, University Clinic of Internal Medicine I, Medical University Vienna, General Hospital Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria. 3. Division of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria. 4. Department of Internal Medicine, University Clinic of Internal Medicine I, Medical University Vienna, General Hospital Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria. 5. Department of Internal Medicine and Oncology, Hospital Rudolfstiftung, Vienna, Austria. 6. Department of Internal Medicine, St. John of God Hospital Vienna, Vienna, Austria.
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. Copyright
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. Copyright
Authors: Christian Dittrich; Robert Königsberg; Martina Mittlböck; Klaus Geissler; Azra Sahmanovic-Hrgovcic; Johannes Pleiner-Duxneuner; Martin Czejka; Philipp Buchner Journal: Invest New Drugs Date: 2018-07-12 Impact factor: 3.850