Protocol title: Effect of acute alcohol consumption on the activity of major cytochrome P450 enzymes, NAT2 and P-glycoprotein. Objectives: The study is mainly conducted to evaluate the effect of acute alcohol consumption on the activity of the most important drug metabolising cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, intestinal CYP3A4, hepatic CYP3A4, NAT2 and on the activity of the drug transporter p-glycoprotein (intestinal and renal). The study should also provide basis for a planned clinical study on interactions caused by chronic alcohol intake. Design: Single center, open-label, two-way, cross-over study with randomly allocated sequences Test-Reference or Reference-Test. The study is not a clinical drug study according to the German Drug Act. Clinical phase: Not applicable Volunteers: 16 healthy male and female subjects are planned for completion in accordance with the protocol, i.e. with evaluable/analysable data for all periods and treatments. Clinical centre: Department of Pharmacology, Clinical Pharmacology Unit (KPH), University of Cologne, Gleueler Str. 24, 50931Köln, Germany
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
16
Department of Pharmacology I, University Hospital Cologne
Cologne, North Rhine-Westphalia, Germany
CYP1A2: AUC0-t of caffeine in plasma
Time frame: 2 months
NAT2 activity: (AFMU + AAMU) / (AFMU + AAMU + 1X + 1U)
Time frame: 2 months
CYP2C9: AUC0-t of tolbutamide in plasma
Time frame: 2 months
CYP2C19: Molar omeprazole / 5-OH-omepazole AUC0-t ratio
Time frame: 2 months
CYP2D6: Molar dextromethorphan / dextrorphan AUC0-t ratio
Time frame: 2 months
Hepatic CYP3A4: hepatic clearance of midazolam
Time frame: 2 months
Intestinal CYP3A4: intestinal extraction of midazolam
Time frame: 2 months
Intestinal p-glycoprotein: absolute bioavailability of digoxin (calculated as Ae)
Time frame: 2 months
Renal p-glycoprotein: renal secretion of digoxin
Time frame: 2 months
CYP1A2: Molar paraxanthine /caffeine AUC0-t ratio
Time frame: 2 months
CYP2C9: Tolbutamide plasma concentration 24 h post-dose
Time frame: 2 months
CYP2C19: AUC0-t of omeprazole in plasma
Time frame: 2 months
CYP2C19: Molar omeprazole / 5-OH-omepazole plasma concentration ratio
Time frame: 2 months
CYP2D6: AUC0-t of dextromethorphan in plasma
Time frame: 2 months
CYP2D6: Molar dextromethorphan / dextrorphan plasma concentration ratio
Time frame: 2 months
Intestinal p-glycoprotein: digoxin Cmax
Time frame: 2 months
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