Clinical study of drug-drug interaction between omeprazole and pyrotinib after meal

Aims We aimed to investigate the effect of omeprazole on the pharmacokinetics (PK) of pyrotinib and determine the safety of this combination in healthy Chinese volunteers. Methods Eighteen healthy volunteers were enrolled in this single-dose and self-controlled study. Pyrotinib (400 mg per oral) was administered 30 minutes after the standard meal. Omeprazole was administered from day 6 (D6) to D10 (40 mg, per oral). On D10, the subjects took omeprazole under fasting conditions, followed by pyrotinib 30 minutes after the standard meal. Blood samples for PK analyses in each phase were collected for analysing the drug concentration. Safety was assessed via clinical laboratory tests and physical examinations. Results Compared with a single dose of pyrotinib, pyrotinib coadministered with omeprazole showed no significant difference in exposure, elimination, half-life and apparent clearance rate. The mixed-effects model revealed that the least-squares geometric mean ratios of area under the concentration-time curve (AUC)(0-t), AUC(0-infinity) and maximum plasma concentration (C(max,)90% confidence intervals) of pyrotinib alone and pyrotinib coadministered with omeprazole were 0.94 (0.82, 1.08), 0.94 (0.83, 1.08) and 0.91 (0.806, 1.038), respectively, indicating the absence of significant differences in AUC(0-t), AUC(0-infinity) and C-max. During the treatment period, 6 subjects (33.3%) reported 8 adverse events during pyrotinib monotherapy and omeprazole administration, respectively; 10 subjects (55.6%) reported 34 adverse events in the combined administration phase. Conclusion Omeprazole, a proton-pump inhibitor, did not significantly impact the PK properties of pyrotinib, and a good safety profile was observed on coadministration.