Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes

Not Applicable

Terminated

• Conditions: Cytochrome P450 Phenotype and Genotype Metrics
• Interventions: Drug: Omeprazole, losartan, caffeine; Drug: Tramadol, omeprazole, losartan, caffeine; Drug: Tramadol

• Registration Number: NCT00981929
• Lead Sponsor: University of Southern Denmark

Brief Summary

The Cytochrome P450 enzymes are responsible for the metabolism of a wide range of drugs and other xenobiotics. Genetic variants of the encoding P450 genes have shown to influence the rate of metabolism of many clinically used drugs.

The drugs tramadol, omeprazole, losartan, quinidine and caffeine reflect the activity of CYP2D6 (tramadol), CYP2C19 (omeprazole), CYP2C9 (losartan), CYP1A2 (caffeine) and CYP3A4/5 (quinidine).

The aim of the study is to investigate if the cocktail of tramadol, omeprazole, losartan and caffeine can be used to simultaneously determine the activity of CYP2D6, CYP2C19, CYP2C9 and CYP1A2. Furthermore, will the natural occurring 4-beta-hydroxy-cholesterol in the blood be measured as a metric for CYP3A4/5.

The study is divided in two. First part will include 12 healthy volunteers and consists of three arms separated by at least one week. In the first arm 50 mg of tramadol will be ingested and urine will be collected for 8 hours. In the second arm 20 mg omeprazole, 25 mg losartan and 200 mg caffeine will be ingested followed by 8 hours urine collection and a blood sample 4 hours after administration of the drugs. In the last arm 50 mg of tramadol, 20 mg omeprazole, 25 mg losartan and 200 mg caffeine will be ingested followed by 8 hours urine collection and a blood sample 4 hours after administration of the drugs.

Metabolic ratios will be calculated based on urine and plasma concentrations of the drugs and the relevant metabolites. Relevant genetic variants of the cytochrome P450 encoding genes will be determined.

If the metabolic ratios of the drugs are not significantly different between the arms, Second part of the study will be conducted.

This part is identical with the last arm and will include a maximum of 400 healthy volunteers: 50 mg of tramadol, 20 mg omeprazole, 25 mg losartan and 200 mg caffeine will be ingested followed by 8 hours urine collection and a blood sample 4 hours after administration of the drugs.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09
• Study First Submitted: 2009-09-21
• Study First Submitted QC: 2009-09-21
• Study First Posted: 2009-09-22
• Primary Completion: 2009-12
• Status Verified: 2010-06
• Last Update Submitted: 2010-06-24
• Last Update Posted: 2010-06-28
• Study Completion: 2011-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 412

Inclusion Criteria

• Healthy volunteers,
• Written consent, AND
• Age 18-65 years old.

Exclusion Criteria

• Daily medication,
• Alcohol abuse,
• Pregnancy, OR
• Breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Omeprazole, losartan, caffeine	Omeprazole, losartan, caffeine	CYP2C19, CYP2C9 and CYP1A2 metrics
Tramadol, omeprazole, losartan and caffeine	Tramadol, omeprazole, losartan, caffeine	CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics
Tramadol	Tramadol	CYP2D6 metric

Primary Outcome Measures

Name	Time	Method
Metabolic ratios	January 2011

Secondary Outcome Measures

Name	Time	Method
Genetic variants	January 2011

Trial Locations

Locations (1)

University of Southern Denmark, Clinical Pharmacology; 🇩🇰 Odense, Fyn, Denmark