Development of Minidose Inje Cocktail Method for Simultaneous Evaluating Five Cytochrome P450 Isoforms in Human

Development of High-throughput Minidose Inje Cocktail Method for Simultaneous Evaluating Five Cytochrome P450 Isoforms in Human

The investigators objectives were developing mini dose five-drug cocktail regimen to evaluate potential drug-drug interactions associated with use of a cocktail of caffeine, losartan, omeprazole, dextromethorphan, and midazolam for simultaneous assessment of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A activities.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Omeprazole; Drug: Cocktail; Drug: Losartan; Drug: Dextromethorphan; Drug: Caffeine; Drug: Midazolam

Detailed Description

The investigators objectives were developing minidose five-drug cocktail regimen to evaluate potential drug-drug interactions associated with use of a cocktail of caffeine, losartan, omeprazole, dextromethorphan, and midazolam for simultaneous assessment of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A activities.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subject whose CYP2C9, CYP2C19, CYP2D6 genotype was determined

Exclusion Criteria:

• Subject who has abnormal laboratory test results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Omeprazole	Drug: Omeprazole; Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days.; Other Names: The drug was made by Yuhan corp.; The drug was exclusively made for this study.; Drug: Cocktail; Group A : Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days. Group B : Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: All of the drugs were made by Yuhan corp.; All of the drugs were exclusively made for this study.
Active Comparator: Losartan	Drug: Cocktail; Group A : Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days. Group B : Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: All of the drugs were made by Yuhan corp.; All of the drugs were exclusively made for this study.; Drug: Losartan; Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days.; Other Names: The drug was made by Yuhan corp.; The drug was exclusively made for this study.
Active Comparator: Midazolam	Drug: Cocktail; Group A : Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days. Group B : Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: All of the drugs were made by Yuhan corp.; All of the drugs were exclusively made for this study.; Drug: Midazolam; Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: The drug was made by Yuhan corp.; The drug was exclusively made for this study.
Active Comparator: Dextromethorphan	Drug: Cocktail; Group A : Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days. Group B : Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: All of the drugs were made by Yuhan corp.; All of the drugs were exclusively made for this study.; Drug: Dextromethorphan; Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days.; Other Names: The drug was made by Yuhan corp.; The drug was exclusively made for this study.
Active Comparator: Caffeine	Drug: Cocktail; Group A : Thirteen healthy male subjects were given oral doses of 200 μg omeprazole, 2 mg losartan and 2 mg dextromethorphan individually and in combination of five drugs (cocktail) every other days. Group B : Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: All of the drugs were made by Yuhan corp.; All of the drugs were exclusively made for this study.; Drug: Caffeine; Thirteen healthy male subjects received 100 μg midazolam and 2 mg caffeine individually followed by five-drugs cocktail every two days.; Other Names: The drug was made by Yuhan corp.; The drug was exclusively made for this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax, AUC	0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 hours post-dose

Collaborators and Investigators

• Sponsor: Inje University
• Investigators: Principal Investigator: Jae Gook Shin, MD, PhD, Inje University

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: December 6, 2011
• First Submitted That Met QC Criteria: April 1, 2012
• First Posted (Estimate): April 4, 2012

Study Record Updates

• Last Update Posted (Estimate): April 4, 2012
• Last Update Submitted That Met QC Criteria: April 1, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Respiratory System Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Antitussive Agents; Midazolam; Dextromethorphan; Losartan; Caffeine; Omeprazole
• Other Study ID Numbers: 10-152