The Effect of Dicloxacillin on Oral Absorption of Drugs
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change in Area under the curve (AUC) of dabigatran
研究概览
简要总结
Worldwide there is an increase in antibiotic resistance which may have fatal long-term consequences. This is due to extensive use and sometimes misuse of antibiotics in the treatment of harmless infections.
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). In this study it will also be investigated whether dicloxacillin induces its own metabolism.
The hypothesis is based on a previous in vivo study showing that rifampicin induces the intestinal P-gp transporter, through activation of the pregnane X receptor (PXR). Dicloxacillin also activates the PXR receptor in vitro, which could result in an induction of P-gp in vivo.
Trial subjects will ingest dicloxacillin for 30 days and at day 10 and 28 ingest dabigatran etexilate to determine if the P-gp transporter has been induced. Plasma and urine will be drawn over 32 hours to determine the concentration of dabigatran.
Change in dicloxacillin concentration will also be measured at day 9 and 27 to establish if dicloxacillin induces its own metabolism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-55 years
- •The following data must be in the normal range or only clinical insignificantly different from this: Estimated glomerular filtration rate (eGFR), alanine aminotransferase (ALAT), bilirubin, HbA1c, hemoglobin
- •BMI >18.5 and < 30 kg/m2
- •Bodyweight ≥ 50 kg
- •Non-smoker (abstained from smoking minimum 2 weeks before the first study day and during the trial)
- •Generally healthy
- •Willing to give informed consent
排除标准
- •Known sensitivity to any of the used drugs or any excipients listed in section 6.1 in the Summary of Product Characteristics (SmPC)
- •Participating in any other intervention trials
- •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 Cytochrome P450 (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)
- •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
研究组 & 干预措施
Dicloxacillin treatment
The investigators measure the concentration of dicloxacillin after 9 and 27 days and the concentration of dabigatran after 10 and 28 days of continuously taking dicloxacillin.
干预措施: Dicloxacillin (Drug)
结局指标
主要结局
Change in Area under the curve (AUC) of dabigatran
时间窗: Baseline and day 28
Change in the activity of the drug transporter P-gp
次要结局
- Change in T1/2 of the metabolite of dicloxacillin(Day 9 and 27)
- Change in AUC of relevant metabolites of dabigatran etexilate(Day 10 and 28)
- Change in Cmax of relevant metabolites of dabigatran etexilate(Day 10 and 28)
- Change in Tmax of relevant metabolites of dabigatran etexilate(Day 10 and 28)
- Change in AUC of the metabolite of dicloxacillin(Day 9 and 27)
- Change in Tmax of dicloxacillin(Day 9 and 27)
- Change in exosome-derived biomarkers(10 and 28)
- Change in Peak Plasma concentration (Cmax) of dabigatran(Day 10 and 28)
- Change in Time to reach Cmax (Tmax) of dabigatran(Day 10 and 28)
- Change in renal clearance (CLr) of dabigatran(Day 10 and 28)
- Change in Elimination half-life (T1/2) of dabigatran(Day 10 and 28)
- Change in Cmax of dicloxacillin(Day 9 and 27)
- Change in CLr of the metabolite of dicloxacillin(Day 9 and 27)
- Change in T1/2 of dicloxacillin(Day 9 and 27)
- Change in CLr of relevant metabolites of dabigatran etexilate(Day 10 and 28)
- Change in T1/2 of relevant metabolites of dabigatran etexilate(Day 10 and 28)
- Change in Cmax of the metabolite of dicloxacillin(Day 9 and 27)
- Change in CLr of dicloxacillin(Day 9 and 27)
- Change in AUC of dabigatran(Day 10 and 28)
- Change in AUC of dicloxacillin(Day 9 and 27)
- Change in Tmax of the metabolite of dicloxacillin(Day 9 and 27)
- Change in biomarkers of drug metabolism enzymes and transporters (DMET)(10 and 28)