Effects of Proton Pump Inhibitor Coadministration on the Plasma Concentration of Erlotinib in Patients With Non-Small...

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.

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).

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 < 0.01]. The C/D ratios of erlotinib in the PPI and H2RB groups were lower than that in the control group [0.39 (0.08-0.76) and 0.48 (0.33-0.81) versus 0.51 (0.28-1.28) mcg·mL·mg·kg], where statistical significance was observed between PPI and control groups (P < 0.05). The population pharmacokinetic estimated oral CL/F in the PPI and H2RB groups were higher than that in the control group [5.55 (3.36-14.52) and 4.82 (2.08-6.32) versus 3.95 (2.01-10.44) L/h], where statistical significance was observed between PPI and control groups (P < 0.05).

Plasma concentrations of erlotinib in patients under coadministration of gastric acid suppressants were lower than those without gastric acid suppressants through drug interaction, suppressing the intestinal absorption of erlotinib. The magnitude of this drug interaction was more pronounced in the coadministration of PPI compared with H2RB.