Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

Abstract

Purpose

A microdose drug–drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study.

Patients and methods

Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis.

Results

The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C _max) and area under the curve to the last measurement (AUC _t) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C _max, and 4.07 (micro), 4.33 (regular) for AUC _t. For the induction study, they were 0.26 (micro) and 0.21 (regular) for C _max, and 0.16 (micro) and 0.15 (regular) for AUC _t. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition.

Conclusion

Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.