Metabolic Detoxication, Phase I
Conditions
Keywords
Cytochrome, Phenotyping, Pharmacokinetics
Brief summary
The purpose of this study is to assess how the pharmacokinetic profiles of each drug of a cocktail of six approved drugs (so-called Basel cocktail) change when the cytochrome P450 system is inhibited or induced.
Interventions
DRUGBasel cocktail+(Fluconazole, Ciprofloxacin, Paroxetine)
DRUGBasel Cocktail
DRUGBasel cocktail + Rifampicin
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Male aged between 18 and 35 years (inclusive) at screening. * No clinically significant findings on the physical examination at screening. * Body mass index (BMI) between 18 and 28 kg/m2 (inclusive) and body weight at least 50 kg at screening. * Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg and heart rate (HR) 45-90 bpm (inclusive). * 12-lead electrocardiogram (ECG) without clinically relevant abnormalities at screening. * Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening. * Ability to communicate well with the investigator and to understand and comply with the requirements of the study.
Exclusion criteria
* Known hypersensitivity to any excipients of the drug formulations. * Treatment with another investigational drug within 30 days prior to screening. * History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening. * Positive results from urine drug screen at screening. * Excessive caffeine consumption, defined as \>800 mg per day at screening\*. * African or Hispanic ethnicity. * History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity. * Smoking within the last 3 months prior to screening. * Previous treatment with any prescribed or OTC medications (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended start of study. * Loss of 250 ml or more of blood within 3 months prior to screening. * Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol. * Legal incapacity or limited legal capacity at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration versus time curve from timepoint 0 to 24 h (AUC24h) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
Secondary
| Measure | Time frame |
|---|---|
| Peak Plasma Concentration (Cmax) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Peak Time (Tmax) of the Basel Cocktail in plasma after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Plasma Halflife (t1/2) in the elimination phase of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Area under the concentration in oral fluid versus time curve from timepoint 0 to 24 h (AUC24h) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Area under the concentration in oral fluid versus time curve from timepoint 0 to infinity (AUC0-inf) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Peak Concentration (Cmax) of the Basel Cocktail in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Area under the plasma concentration versus time curve from timepoint 0 to infinity (AUC0-inf) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Halflife (t1/2) in the elimination phase of the Basel Cocktail in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Area under the concentration in dried blood spots versus time curve from timepoint 0 to 24 h (AUC24h) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Area under the concentration in dried blood spots versus time curve from timepoint 0 to infinity (AUC0-inf) of the Basel Cocktail after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Peak Concentration (Cmax) of the Basel Cocktail in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Peak Time (Tmax) of the Basel Cocktail in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Halflife (t1/2) in the elimination phase of the Basel Cocktail in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
| Peak Time (Tmax) of the Basel Cocktail in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. | — |
Countries
Switzerland
Outcome results
None listed