NCT07426042

Effect of Dexamethasone on CYP Enzyme Activity in Healthy Male Subjects

A Clinical Study Evaluating the Effects of Dexamethasone on the Activities of CYP2C9, CYP2C19, and CYP3A4 Substrates in Healthy Male Subjects

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Min Kyu Park · Academic / Other
• Sex: Male
• Age: 19 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Purpose: The purpose of this study is to understand how dexamethasone affects the activity of drug-metabolizing enzymes in the body and how this may influence interactions with other medicines, such as voriconazole. Background: Many medicines are broken down in the body by enzymes called cytochrome P450 (CYP) enzymes. Differences in CYP enzyme activity between individuals can lead to variability in drug response and drug-drug interactions. Dexamethasone is known to affect CYP enzyme activity, and voriconazole is a medication that is metabolized by these enzymes. Participants: This study will include a total of 12 healthy adult male volunteers. Participants will be grouped based on their metabolic status, including 6 normal metabolizers (NM) and 6 poor metabolizers (PM). Interventions: Participants will receive a combination of probe drugs known as a CYP probe cocktail to assess baseline CYP enzyme activity. Dexamethasone will be administered, and the CYP probe cocktail will be given again to evaluate changes in enzyme activity. Voriconazole will be used to assess the potential for drug-drug interactions related to changes in CYP enzyme activity. Blood samples will be collected during the study. Outcome Measures: The main outcomes of this study are changes in blood concentrations of the probe drugs, which reflect changes in CYP enzyme activity, and comparisons of these changes between normal metabolizers and poor metabolizers. Hypothesis: The study hypothesizes that dexamethasone alters CYP enzyme activity and that the magnitude of this effect differs between normal metabolizers and poor metabolizers, potentially affecting the metabolism of drugs such as voriconazole.

Detailed description

This study is designed as an open-label, single-sequence clinical pharmacology study to evaluate the effects of dexamethasone on cytochrome P450 (CYP) enzyme activity in healthy adult male volunteers. CYP enzyme activity will be assessed using a validated CYP probe cocktail consisting of multiple probe substrates administered concurrently to evaluate the functional activity of selected CYP isoforms. The probe cocktail will be administered at baseline to characterize individual CYP enzyme activity prior to dexamethasone exposure. Following baseline assessment, dexamethasone will be administered for a predefined period. After completion of dexamethasone administration, the CYP probe cocktail will be administered again to evaluate changes in CYP enzyme activity induced by dexamethasone. Voriconazole, a CYP-metabolized drug, will be included to assess the potential impact of dexamethasone-induced enzyme modulation on clinically relevant drug-drug interactions. Serial blood samples will be collected after administration of the probe cocktail and voriconazole to determine pharmacokinetic parameters, including maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC). Changes in these parameters before and after dexamethasone administration will be used as indicators of alterations in CYP enzyme activity. Participants will be stratified based on CYP2C19 genotype into normal metabolizers (NM) and poor metabolizers (PM). Comparative analyses will be conducted between these groups to explore the influence of genetic polymorphism on dexamethasone-induced changes in CYP enzyme activity. The results of this study are expected to provide mechanistic insight into dexamethasone-mediated modulation of CYP enzymes and its potential implications for drug-drug interactions involving CYP-metabolized medications.

Conditions

• Drug-Drug Interactions

Interventions

Type	Name	Description
DRUG	Dexamethasone	Dexamethasone will be administered orally to evaluate its effect on cytochrome P450 enzyme activity.
DRUG	CYP Probe Cocktail	A CYP probe cocktail composed of approved, commercially available drugs (caffeine, flurbiprofen, omeprazole, and midazolam) will be administered concomitantly as a single-dose cocktail to phenotypically assess cytochrome P450 enzyme activities before and after dexamethasone administration.
DRUG	voriconazole	Voriconazole will be administered to assess drug-drug interactions associated with changes in cytochrome P450 enzyme activity.

Timeline

• Start date: 2026-04-01
• Primary completion: 2026-05-01
• Completion: 2026-06-01
• First posted: 2026-02-23
• Last updated: 2026-02-23