Flucloxacillin as an inducer of CYP-enzymes

INTERVENTION: 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 number: 500‐ CONDITION: 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 Therapeutic area: Not possible to specify PRIMARY OUTCOME: 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. 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. Secondary Objective: It will be investigated whether or not flucloxacillin induces its own metabolism. Timepoint(s) of evaluation of this end point: After the study is completed and drug analysis is completed. SECONDARY OUTCOME: 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. 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