Healthy volunteers. (Flucloxacillin is used against infections caused by beta-lactamase-producing organisms) Testing for drug-drug interactions caused by flucloxacillin MedDRA version: 20.0 Level: LLT Classification code 10004035 Term: Bacterial infection due to staphylococcus aureus System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Flucloxacillin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FLUCLOXACILLIN
CAS Number: 5250-39-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration
Sponsors
University of Southern Denmark
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-55 years - The following data have to be in the normal range or only clinical insignificantly different from this: eGFR, ALAT, bilirubin, HbA1c, haemoglobin - BMI 18.5 – 29.9 kg m-2 - Non-smoker (abstained from smoking minimum 2 weeks before the first study day and during the trial) - Generally healthy - Willing to give informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Known sensitivity to any of the used drugs or any excipients listed in section 6.1 in the Summary of Product Characteristics (SmPC) - Known allergy towards penicillin or cephalosporines - Any of the following diseases (current or previous): Heart disease, known family history of prolonged QTc interval, sudden death or conditions that might prolonged QTc-intervals, hypotension, severe disturbance of electrolyte balance e.g. hypokalemia or hypomagnesemia, myasthenia gravis, lung- or respiratory diseases, an anatomically abnormality of the respiratory tract, sleep apnea syndrome - Intake of any significant prescription drugs, over-the-counter drugs, herbal drugs or dietary supplements. Contraindicated drugs include: Benzodiazepines, beta blockers, ergot alkaloids, herbal preparations containing St. John’s wort, antiarrhythmics, neuroleptics, antidepressive agents, antibiotics, antifungal agents, non- sedating antihistamines, antimalarials, methadone, elbasvir, grazoprevir, nelfinavir cisapride, pimozide, bepridil - Alcohol abuse or if the Danish Health Authority recommendation regarding alcohol intake has been exceeded 2 weeks before the first study day (men 14 units alcohol/week, women 7 units alcohol/week) - Women who are breastfeeding - Positive pregnancy test at inclusion screening or at any of the study days - Participation in any other interventional trials
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of this study is to investigate if treatment with flucloxacillin increases drug metabolism in healthy volunteers, through induction of cytochrome P450 (CYP) enzymes, CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. ;Secondary Objective: It will be investigated whether or not flucloxacillin induces its own metabolism.;Primary end point(s): The primary endpoint is the change in AUC of the CYP3A4 substrate midazolam, after 28 days of flucloxacillin treatment compared to baseline. ;Timepoint(s) of evaluation of this end point: After the study is completed and drug analysis is completed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in the pharmacokinetics of the six substrates midazolam (substrate of CYP3A4), caffeine (CYP1A2), efavirenz (CYP2B6), losartan (CYP2C9), omeprazole (CYP2C19) and metoprolol (CYP2D6) and their metabolites after 10 and 28 days of flucloxacillin treatment compared to baseline. The concentrations will be determined from plasma and urine samples. Changes in the full pharmacokinetics of flucloxacillin and its metabolite after 9 and 27 days of flucloxacillin treatment compared to baseline. This will be measured as concentrations in plasma and urine samples.;Timepoint(s) of evaluation of this end point: After the study is completed and drug analysis is completed. | — |
Countries
Denmark
Contacts
Public ContactClinical Pharmacology and Pharmacy
Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark
Outcome results
None listed