Effects of omeprazole and esomeprazole on the pharmacokinetics of erlotinib and its metabolite OSI-420 in rats

The purpose of this paper was to research the effect of long-term orally administered omeprazole and esomeprazole on the pharmacokinetics of erlotinib and its major active metabolite, desmethyl erlotinib (OSI-420) in rats. Eighteen healthy male Sprague-Dawley rats were divided into three groups at random: A group (control group, received normal saline for 7 days), B group (4 mg/kg omeprazole for 7 days) and C group (4 mg/kg esomeprazole for 7 days). All the rats were given a single dose of erlotinib (15 mg/kg) after the last administration. The plasma concentration of erlotinib and its major active metabolite, desmethyl erlotinib (OSI-420) were estimated using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and different pharmacokinetic parameters were calculated by DAS 2.0 software. Compared to the control A group, omeprazole (B group) and esomeprazole (C group) significantly decreased the C-max and AUC((0-infinity)) of erlotinib, but increased CLz/F in rats. Moreover, the similar results were observed for the metabolite OSI-420 of erlotinib. These results revealed that omeprazole and esomeprazole have a significant reduction on the absorption of erlotinib. Therefore, it is recommended that the concomitant use of erlotinib with proton pump inhibitors should be avoided.