Dicloxacillin: Clinical Relevance of Drug-drug Interactions by Induction of Drug Metabolism.

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebos; Drug: Dicloxacillin

• Registration Number: NCT02983890
• Lead Sponsor: Per Damkier

Brief Summary

This trial is conducted as a cocktail-study namely an open-label, randomized, two-sequence, two-period crossover, cocktail study where a combination of cocktail-drugs is used to illustrate whether or not, or to what degree dicloxacillin affects the level of activity of the 5 most important CYP enzymes and therefore plays a potentially decisive role in serious drug-drug interactions.

Detailed Description

Given knowledge explains dicloxacillin and the drug warfarin to be a potential dangerous drug drug interaction because the effects of warfarin is downregulated to a degree as to where it might cause patients to have thrombotic events.

A potential explanation to this is namely dicloxacillin increases the activity of certain drug metabolising enzymes metabolising warfaring which in turn decreases the concentration of the drug in the blood and the therapeutic effect.

Cocktail study is the golden standard to investigate as to whether there is changes is P450 enzymes as a result of drug-drug interactions.

The cocktail consists of Midazolam, omeprazole, tolbutamide, caffein and dextromethorphan which is well known markers for these enzymes. These markers are safe, have specific (enzyme) metabolism and has been used in several studies with no Serious Adverse reactions reported.

By measuring the Concentration of the drug and its metabolites in plasma / Urine before and after treatment with dicloxacillin we will estimate AUC (area under the curve) and test our hypothesis/primary end point of whether there is change in AUC for Tolbutamide (CYP2C9)

Study Timeline

• Study Start: 2016-10-06
• Study First Submitted: 2016-11-30
• Study First Submitted QC: 2016-12-05
• Study First Posted: 2016-12-06
• Primary Completion: 2017-04-05
• Study Completion: 2017-10-01
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-21
• Last Update Posted: 2018-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

• Are you in a general healthy condition?; questions asked; Are you healthy in general? 2; Do you have any chronic diseases? 3; Are you taking any medications regularly? 4, Are you taking any medications periodically . 5; Are you taking nutrition supplements, "nature-medicine" or over-the-counter drugs
• BMI; range; 18,5-29,9 kg/m2
• eGFR(estimated glomerular filtration rate), ALAT(alanine aminotransferase), bilirubin, hæmoglobin og HbA1c, should be within normal limits or without clinically significantly deviation from these.
• Non-Smoker

Exclusion Criteria

• Hypersensitivity to applied medications. Known allergy to penicillin or type 1-reaction to cefalosporins.
• Known allergy to sulfonamides
• Clinically relevant intake of receipt-required medication, over-the-counter medication or nutritional supplements.
• Chronic or daily intake of alcohol.
• Participation in other Intervention-studies

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm of study 2	Placebos	No treatment
Arm of study1	Dicloxacillin	Dicloxacillin tablets.

Primary Outcome Measures

Name	Time	Method
AUC(area under the curve) for tolbutamid (CYP2C9), as a result of dicloxacillin-treatment	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.	AUC measurements giving an estimate of activity og the relevant enzymes.

Secondary Outcome Measures

Name	Time	Method
*AUC(area under the curve) for midazolam (CYP3A4) and dextromethorphan (CYP1A2) omeprazole (CYP2C19) and caffein (CYP1A2)	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
Clearance	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.	The volume of plasma from which the drug is completely removed per unit time. Reflects rate of drug elimination divided by plasma concentration.
T(max)	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.	The amount of time that the drug is present at the maximum concentration in serum.
C(max) (peak plasma concentration)	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.	The peak serum concentration of a therapeutic drug.

Trial Locations

Locations (1)

Klinisk Biokemisk Farmakologi syddansk universitet; 🇩🇰 Odense, Funen, Denmark