Effects of Proton Pump Inhibitor Coadministration on the Plasma Concentration of Erlotinib in Patients With Non-Small Cell Lung Cancer.
作者： Masahiro Ohgami , Takayuki Kaburagi , Atsuhiko Kurosawa , Kosuke Doki , Toshihiro Shiozawa
DOI: 10.1097/FTD.0000000000000552
关键词:
摘要: BACKGROUND Erlotinib is used for treating non-small cell lung cancer (NSCLC). Intestinal absorption of erlotinib impaired under gastric pH elevation; therefore, coadministration acid suppressants may provide lower blood concentration erlotinib. We investigated the effects with proton pump inhibitors (PPIs) and histamine H2 receptor blockers (H2RBs) on plasma erlotinib-induced adverse reaction in patients NSCLC. METHODS Forty-two receiving therapy NSCLC were recruited this study. Association reactions (rash diarrhea) was examined. Plasma concentration-to-dose (C/D) ratios oral clearance (CL/F), which estimated by population pharmacokinetic analysis concentrations erlotinib, compared among 3 patient groups: without (control group), PPI (PPI H2RB (H2RB group). RESULTS Patients grade ≥2 rash had higher those ≤1 [1.02 (0.43-2.60) versus 0.67 (0.10-1.85) mcg/mL, P < 0.01]. The C/D groups than that control group [0.39 (0.08-0.76) 0.48 (0.33-0.81) 0.51 (0.28-1.28) mcg·mL·mg·kg], where statistical significance observed between (P 0.05). CL/F [5.55 (3.36-14.52) 4.82 (2.08-6.32) 3.95 (2.01-10.44) L/h], CONCLUSIONS through drug interaction, suppressing intestinal magnitude interaction more pronounced H2RB.
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