Healthy volunteers. (Dicloxacillin is used against infections caused by beta-lactamase-producing organisms) Testing for drug-drug interactions caused by dicloxacillin. MedDRA version: 20.0 Level: LLT Classification code 10004035 Term: Bacterial infection due to staphylococcus aureus System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Dicillin
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: DICLOXACILLIN
CAS Number: 3116-76-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500
Sponsors
Odense University Hosipital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-55 years - The following data must be in the normal range or only clinical insignificantly different from this: eGFR, ALAT, bilirubin, HbA1c, hemoglobin - BMI >18.5 and =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). - Intake of any significant prescription drugs, over-the-counter drugs, herbal drugs, or dietary supplements*. Contraindicated drugs include: Anticoagulants, antiplatelet aggregation medicinal products, ticagrelor, clopidogrel, acetylsalicylic acid, chronic NSAIDs use, amiodarone, verapamil, systemic ketoconazole, clarithromycin, cyclosporin, itraconazole, tacrolimus, posaconazole, dronedarone, glecaprevir/pibrentasvir, quinidine, ritonavir, digoxin, selective serotonin reuptake inhibitors (SSRIs), selective serotonin norephinephrine reuptake inhibitors (SNRIs), pantoprazole, ranitidine, previous use of dicloxacillin or other P-gp or CYP450 inhibitors/inducers within 4 weeks prior to the start of treatment, probenecid, tetracycline, methotrexate - 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 unites alcohol/week) - Participating in any other intervention trials - A positive pregnancy test at inclusion screening or any of the study days - Known penicillin allergy or reactions against cephalosporins, cephamycin, 1-oxa-ß-lactamer, or carbapenems - Women who are breastfeeding - Diagnosis of any of the following diseases (current or previous): Mechanical heart valve, congenital or acquired coagulation disorders, thrombocytopenia or functional platelet defects, biopsy within 4 weeks, major trauma, bacterial endocarditis, esophagitis, gastritis, gastroesophageal reflux, active meningitis, encephalitis, intracranial abscess, undergoing surgery, liver disease, history of thrombosis or diagnosed with antiphospholipid syndrome, active cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim of this study is to investigate if treatment with dicloxacillin can lead to drug-drug interactions through induction of the efflux transporter P-glycoprotein (P-gp). ;Secondary Objective: It will be investigated whether or not dicloxacillin induces its own metabolism. ;Primary end point(s): The primary endpoint is the change in AUC of the P-gp substrate dabigatran after 28 days of dicloxacillin treatment compared to baseline. ;Timepoint(s) of evaluation of this end point: After the drug analysis is completed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in the full pharmacokinetics of the P-gp substrate dabigatran etexilate and all relevant metabolites after 10 and 28 days of dicloxacillin treatment compared to baseline. The concentrations will be determined from plasma and urine samples. Changes in the full pharmacokinetics of dicloxacillin and its metabolites after 9 and 27 days of dicloxacillin treatment compared to baseline. This will be measured as concentrations in plasma and urine samples. Changes in biomarkers of DMET after 10 and 28 days of dicloxacillin treatment compared to baseline. Changes in exosome-derived biomarkers after 10 and 28 days of dicloxacillin treatment compared to baseline. ;Timepoint(s) of evaluation of this end point: After the drug analysis is completed | — |
Countries
Denmark
Contacts
Public ContactClinical Pharmacology and Pharmacy
Clinical Pharmacology, Pharmacy and Environmental Medicine, Institure of Publich Health, University of Southern Denmark
Outcome results
None listed