Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- ratio of atorvastatin AUC0-8 between groups
研究概览
简要总结
Altered bioavailability of drugs will potentially affect both drug efficacy as well as safety. In patients subjected to bariatric surgery due to morbid obesity the gastro intestinal tract is considerably reconstructed and a change in drug bioavailability is very likely. Getting further knowledge on important mechanisms responsible for altered bioavailability would help in predicting clinically relevant consequences on different drugs.
In the present study we aim to investigate the effect of bariatric surgery on atorvastatin bioavailability. Atorvastatin is subjected to both extensive metabolism and drug transport and will potentially be a good predictor for mechanisms relevant for other drugs as well.
In addition will the expression of different enzymes and transporters be measured in the gastrointestinal tract and in the liver to elucidate on mechanism behind the eventual effects.
详细描述
The primary objective of the study is to compare the effect of gastric bypass and BPD+DS operations on atorvastatin bioavailability.
Secondary objectives are to determine the relative change in atorvastatin bioavailability following gastric bypass as well as BPD+DS operations. In addition will the individual CYP3A4, CYP3A5 and P-gp activity in the different organs from where biopsies can be obtained be descriptively compared with atorvastatin pharmacokinetic variables.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Scheduled for bariatric surgery.
- •18 years of age or older.
- •Ongoing treatment with statin.
- •Able and willing to donate GI-tract and liver biopsies.
- •Signed informed consent.
排除标准
- •Concomitant treatment with drugs and/or other factors that may influence atorvastatin pharmacokinetics
研究组 & 干预措施
Surgery
Bariatric surgery
干预措施: Bariatric surgery (Procedure)
结局指标
主要结局
ratio of atorvastatin AUC0-8 between groups
时间窗: june 2009
次要结局
- Descriptive listing of atorvastatin and metabolites concentrations in patients with different genotypes analyzed. It is anticipated that an exploratory analysis will be performed to compare the groups.(june 2009)
- Descriptive listing of the relationship between plasma and skeletal muscle as well as adipose tissue concentrations of atorvastatin and metabolites.(december 2009)
- Change in bioavailability of atorvastatin within each surgical technique will be analyzed as ratio of AUC0-8 from before to after surgery in accordance to the bioequivalence criteria of 80-125%.(june 2009)
- Descriptive comparison of protein expression of CYP3A4, CYP3A5 and P-gp in different biopsies and atorvastatin and its metabolites pharmacokinetics.(december 2009)
- Adverse events and serious adverse events will be listed.(june 2009)
- Descriptive comparison of mRNA expression of CYP3A4, CYP3A5, P-gp and OATP1B1 in different biopsies and atorvastatin and metabolites pharmacokinetics.(june 2009)