Effects of omeprazole on the pharmacokinetics and toxicities of irinotecan in cancer patients: A prospective open-label cross-over drug-interaction study

2502 Background: The proton pump inhibitor omeprazole (Losec) is one of the most extensively prescribed medications worldwide and within its class, omeprazole is most frequently associated with drug interactions. In vitro studies have shown that omeprazole can alter the function of metabolic enzymes and efflux transporters that are involved in the metabolism of irinotecan, such as UGT1A1, CYP3A, and ABCC2. In this open-label cross-over study we investigated the effects of omeprazole on the pharmacokinetics and toxicities of irinotecan. Methods: Fourteen patients were treated with one course (C1) of single agent irinotecan (600 mg i.v., 90 min) followed three weeks later by a second course (C2) with concurrent use of omeprazole 40 mg once daily, which was started 2 weeks prior to C2. Plasma samples were obtained up to 55 hours after infusion and analyzed for irinotecan, and its metabolites SN-38, SN-38 glucuronide (SN-38G), NPC, and APC by reversed-phase high-performance liquid chromatography with fluoresc...