Effect of Dexamethasone on CYP Enzyme Activity in Healthy Male Subjects
ConditionDrug-Drug Interactions
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexMale
Age19-50
SponsorMin Kyu Park
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy male volunteers aged 19 to 50 years, inclusive, at the time of screening.
Body weight between 50.0 kg and 90.0 kg, and body mass index (BMI) between 18.5 kg/m² and 29.9 kg/m² at the time of screening.
Subjects with a CYP2C19 genotype classified as either normal metabolizers (*1/*1) or poor metabolizers (*2/*2, *2/*3, 3/3) based on genotyping results.
Subjects who have received sufficient explanation of the study, fully understood the study procedures, voluntarily agreed to participate, and provided written informed consent prior to any study-related procedures.
Disqualifiers
Subjects with any clinically significant disease or medical history involving the hepatobiliary, renal, neurological, immunological, respiratory, gastrointestinal, endocrine, hematologic/oncologic, cardiovascular (including heart failure and Torsades de pointes), urogenital, psychiatric (including mood disorders and obsessive-compulsive disorder), or sexual dysfunction systems.
Subjects with a history of gastrointestinal diseases (e.g., Crohn's disease, ulcer, gastritis, gastric spasm, gastroesophageal reflux disease) or gastrointestinal surgery that may affect the safety or pharmacokinetics of the investigational products, except for uncomplicated appendectomy or hernia repair.
Subjects with known hypersensitivity or clinically significant allergic reactions to any components of the investigational products or to other drugs (e.g., aspirin, antibiotics).
Subjects with hereditary disorders, including sucrase-isomaltase deficiency, galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
Trial design
Design model
Single group
Treatments tested in this trial
Dexamethasone
DrugDexamethasone will be administered orally to evaluate its effect on cytochrome P450 enzyme activity.
CYP Probe Cocktail
DrugA 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.
voriconazole
DrugVoriconazole will be administered to assess drug-drug interactions associated with changes in cytochrome P450 enzyme activity.
Treatment groups
12 Participants
are divided into 1 treatment groupGroup A: Single GroupExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Cmax of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen)
Cmax of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen) will be assessed to evaluate the effects of dexamethasone on cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 for voriconazole; Period 2 Day 8 for midazolam, omeprazole, and flurbiprofen)2
AUClast of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen)
AUClast of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen) will be assessed to evaluate the effects of dexamethasone on cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 for voriconazole; Period 2 Day 8 for midazolam, omeprazole, and flurbiprofen)3
AUCinf of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen)
AUCinf of CYP Probe Substrates(Voriconazole, Midazolam, Omeprazole, Flurbiprofen) will be assessed to evaluate the effects of dexamethasone on cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 for voriconazole; Period 2 Day 8 for midazolam, omeprazole, and flurbiprofen)Secondary outcomes
1
Tmax of Perpetrator(Dexamethasone)
Tmax of Perpetrator(Dexamethasone) will be assessed to evaluate the effects of cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4 on dexamethasone, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 )2
Cmax of Perpetrator(Dexamethasone)
Cmax of Perpetrator(Dexamethasone) will be assessed to evaluate the effects of cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4 on dexamethasone, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 )3
AUCtau of Perpetrator(Dexamethasone)
AUCtau of Perpetrator(Dexamethasone) will be assessed to evaluate the effects of cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4 on dexamethasone, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 )4
t1/2 of Perpetrator(Dexamethasone)
t1/2 of Perpetrator(Dexamethasone) will be assessed to evaluate the effects of cytochrome P450 enzyme activity, specifically CYP2C9, CYP2C19, and CYP3A4 on dexamethasone, in healthy adult male subjects.
Time frame
Up to the last PK sampling time (Period 2 Day 9 )Locations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Min Kyu Park
Lead sponsor
Chungbuk National University Hospital
Sponsor institution
Source ClinicalTrials.gov
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