Induction of Drug Metabolism: In Vivo Comparison of Carbamazepine and Oxcarbazepine.

Induction of Drug Metabolism: A Comparative, Pharmacokinetic in Vivo Study of the Effect of Carbamazepine and Oxcarbazepine on CYP3A4.

This is a study of the possible effect of two antiepileptic drug on enzymes in the liver that metabolizes a number of drugs. It is a well know fact that carbamazepine induces some of these enzymes and this may reduce the effect of concomitantly administered drugs. Clinical observations suggest that oxcarbazepine does not induce these enzymes to the same degree.

This study directly compares the ability of these two drugs to induce the cytochrome P450 3A4 enzyme, in healthy volunteers using a well defined biomarker reaction of a specific enzyme activity.

It is the hypothesis that oxcarbazepine induces CYP3A4 to a lesser degree than carbamazepine.

Study Overview

• Status: Completed
• Conditions: Metabolic Clearance Rate
• Intervention / Treatment: Drug: carbamazepine oxcarbazepine

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark, 5210
    • University of Southern Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• BMI < 30
• Non smoker
• No signs or symptoms of disease by routine laboratory analysis, ECG and physical examination (general appearance assessment; pulmonal and cardiac stetoscopy; abdominal palpation)
• Informed consent

Exclusion Criteria:

• signs or symptoms of disease by routine laboratory analysis, ECG and physical examination
• mental disease
• participation in another clinical trial involving drugs with 3 months of randomization
• donation of more than 500 mL blood within 3 months of randomization
• intake of more than 21 alcohol equivanlents (one normal strength beer contain one alcohol equivalent)per week

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Formation clearance of 3-hydroxyquinidine

Secondary Outcome Measures

Outcome Measure
Ratio of metabolite to drug AUC's of 3-OH quinidine to quinidine.

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Novartis; Danish Research Agency
• Investigators: Principal Investigator: Per Damkier, MD, Ph.D., Odense University Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): October 1, 2006
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: November 28, 2005
• First Submitted That Met QC Criteria: November 28, 2005
• First Posted (Estimate): December 1, 2005

Study Record Updates

• Last Update Posted (Estimate): April 22, 2015
• Last Update Submitted That Met QC Criteria: April 21, 2015
• Last Verified: March 1, 2005

More Information

Terms related to this study

• Keywords: Human; CYP3A4; Carbamazepine; Induction; Oxcarbazepine; Quinidine; In vivo
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Carbamazepine; Oxcarbazepine
• Other Study ID Numbers: AKF-315