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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02983890
• Other study ID #: AKF-388
• Status: Completed
• Phase: Phase 1
• Start date: October 6, 2016
• Est. completion date: October 1, 2017

Study information

• Verified date: August 2018
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: October 1, 2017
• Est. primary completion date: April 5, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Dicloxacillin
Tablets containing dicloxacillin are taken 500mg 2x 3 times per day, for 10 days. Followed by test-day nr 1 at day 11. Both arms receives both treatments, randomly assigned
• Placebos
No drug are taken for 10 days. Non-blinded. Followed by test-day nr 1 at day 11. Both arms receives both treatments, randomly assigned

Locations

Country	Name	City	State
Denmark	Klinisk Biokemisk Farmakologi syddansk universitet	Odense	Funen

Sponsors (1)

Lead Sponsor	Collaborator
Per Damkier

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC(area under the curve) for tolbutamid (CYP2C9), as a result of dicloxacillin-treatment	AUC measurements giving an estimate of activity og the relevant enzymes.	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
Secondary	*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.
Secondary	T(max)	The amount of time that the drug is present at the maximum concentration in serum.	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
Secondary	C(max) (peak plasma concentration)	The peak serum concentration of a therapeutic drug.	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
Secondary	Clearance	The volume of plasma from which the drug is completely removed per unit time. Reflects rate of drug elimination divided by plasma concentration.	Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.