Influence of Anticonvulsants on the Metabolism and Elimination of Irinotecan
August 01, 2002
The hepatic metabolism and biliary secretion of irinotecan (CPT-11, Camptosar) and metabolites is complex and involves cytochrome P450 isoenzymes, carboxylesterases, glucuronosyltransferase, and the ATP-dependent export pumps MRP-2 and MXR. Enzyme-inducing antiepileptic drugs (EIAEDs) such as phenytoin and carbamazepine are known to induce several of the metabolic pathways relevant to ininotecan’s elimination. The North American Brain Tumor Consortium phase I study is designed to determine the maximum tolerated dose and pharmacokinetics of irinotecan given every 3 weeks to patients who are receiving EIAEDs.