Effects of Proton Pump Inhibitor Coadministration on the Plasma Concentration of Erlotinib in Patients With Non–Small Cell Lung Cancer

Background: Erlotinib is used for treating non–small cell lung cancer (NSCLC). Intestinal absorption of erlotinib is impaired under gastric pH elevation; therefore, coadministration of gastric acid suppressants may provide lower blood concentration of erlotinib. We investigated the effects of erlotinib coadministration with proton pump inhibitors (PPIs) and histamine H2 receptor blockers (H2RBs) on the plasma concentration of erlotinib and erlotinib-induced adverse reaction in patients with NSCLC. Methods: Forty-two patients receiving erlotinib therapy for NSCLC were recruited for this study. Association of adverse reactions (rash and diarrhea) with plasma concentration of erlotinib was examined. Plasma concentration-to-dose (C/D) ratios and oral clearance (CL/F), which was estimated by population pharmacokinetic analysis of plasma concentrations of erlotinib, were compared among 3 patient groups: without coadministration of gastric acid suppressants (control group), with coadministration of PPI (PPI group), and coadministration of H2RB (H2RB group). Results: Patients with grade ≥2 rash had higher plasma concentrations of erlotinib compared with those with grade ≤1 [1.02 (0.43–2.60) versus 0.67 (0.10–1.85) mcg/mL, P
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research