Anti-cancer drugs
-
Randomized Controlled Trial
Effect of gastric pH on erlotinib pharmacokinetics in healthy individuals: omeprazole and ranitidine.
The aim of this study was to evaluate the effect of coadministration of acid-reducing agents on the pharmacokinetic exposure of orally administered epidermal growth factor receptor inhibitor erlotinib, a drug that displays pH-dependent solubility. Two studies were conducted, the first with the proton pump inhibitor omeprazole and the second with the H2-receptor antagonist ranitidine. Twenty-four healthy male and female volunteers were enrolled in each study. ⋯ Erlotinib pharmacokinetic exposure was substantially reduced upon coadministration with omeprazole and ranitidine, but not when administered with a staggered dosing approach to ranitidine. Therefore, it is recommended that the concomitant use of erlotinib with proton pump inhibitors be avoided. If treatment with an H2-receptor antagonist such as ranitidine is required, erlotinib must be administered 10 h after the H2-receptor antagonist dosing and at least 2 h before the next dose of the H2-receptor antagonist.