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

Per Damkier

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: Placebos

Drug: Dicloxacillin

Study type

Interventional

Funder types

Other

Identifiers

NCT02983890

AKF-388

Details and patient eligibility

About

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.

Full 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)

Enrollment

12 patients

Sex

Male

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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