Cytochrome P450 Phenotype and Genotype Metrics Clinical Trial
Official title:
Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes
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.
n/a
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Screening