Dicloxacillin: Clinical Relevance of Drug-drug Interactions by Induction of Drug Metabolizing Enzymes.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- AUC(area under the curve) for tolbutamid (CYP2C9), as a result of dicloxacillin-treatment
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm of study1
Dicloxacillin tablets.
干预措施: Dicloxacillin (Drug)
Arm of study 2
No treatment
干预措施: Placebos (Drug)
结局指标
主要结局
AUC(area under the curve) for tolbutamid (CYP2C9), as a result of dicloxacillin-treatment
时间窗: 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.
次要结局
- *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.)
- T(max)(Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.)
- 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.)
- Clearance(Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.)
研究者
Per Damkier
Professor, head consultant, MD, ph.d.
Odense University Hospital