Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes
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|ClinicalTrials.gov Identifier: NCT00981929|
Recruitment Status : Terminated (Unexpected non-serious adverse events)
First Posted : September 22, 2009
Last Update Posted : June 28, 2010
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.
|Condition or disease||Intervention/treatment||Phase|
|Cytochrome P450 Phenotype and Genotype Metrics||Drug: Tramadol Drug: Omeprazole, losartan, caffeine Drug: Tramadol, omeprazole, losartan, caffeine||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||412 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes|
|Study Start Date :||September 2009|
|Estimated Primary Completion Date :||December 2009|
|Estimated Study Completion Date :||January 2011|
Active Comparator: Tramadol
50 mg single oral dose
Active Comparator: Omeprazole, losartan, caffeine
CYP2C19, CYP2C9 and CYP1A2 metrics
Drug: Omeprazole, losartan, caffeine
20 mg omeprazole 25 mg losartan 200 mg caffeine
Active Comparator: Tramadol, omeprazole, losartan and caffeine
CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics
Drug: Tramadol, omeprazole, losartan, caffeine
50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine
- Metabolic ratios [ Time Frame: January 2011 ]
- Genetic variants [ Time Frame: January 2011 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00981929
|University of Southern Denmark, Clinical Pharmacology|
|Odense, Fyn, Denmark, D-5000|