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

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Park GJ, Bae SH, Park WS, Han S, Park MH, Shin SH, Shin YG, Yim DS

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

Drug Des Devel Ther. 2017 Mar 30;11:1043-1053. doi: 10.2147/DDDT.S131797. eCollection 2017.

PubMed ID

28408803 [ View in PubMed

]

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 mug, 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 (Cmax) and area under the curve to the last measurement (AUCt) 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 Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16 (micro) and 0.15 (regular) for AUCt. 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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Rifampicin	Cytochrome P450 2C19	Protein	Humans	Unknown	Inducer	Details

Drug Interactions

Drugs	Interaction
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