Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Open Label
|Official Title:||Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin|
- ratio of atorvastatin AUC0-8 between groups [ Time Frame: june 2009 ] [ Designated as safety issue: No ]
- 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%. [ Time Frame: june 2009 ] [ Designated as safety issue: No ]
- Descriptive comparison of mRNA expression of CYP3A4, CYP3A5, P-gp and OATP1B1 in different biopsies and atorvastatin and metabolites pharmacokinetics. [ Time Frame: june 2009 ] [ Designated as safety issue: No ]
- Descriptive comparison of protein expression of CYP3A4, CYP3A5 and P-gp in different biopsies and atorvastatin and its metabolites pharmacokinetics. [ Time Frame: december 2009 ] [ Designated as safety issue: No ]
- 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. [ Time Frame: june 2009 ] [ Designated as safety issue: No ]
- Descriptive listing of the relationship between plasma and skeletal muscle as well as adipose tissue concentrations of atorvastatin and metabolites. [ Time Frame: december 2009 ] [ Designated as safety issue: No ]
- Adverse events and serious adverse events will be listed. [ Time Frame: june 2009 ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2006|
|Study Completion Date:||December 2010|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Procedure: Bariatric surgery
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00331565
|Hospital in Vestfold|
|Tønsberg, Norway, 3103|
|Principal Investigator:||Rune Sandbu, MD, PhD||Hospital in Vestfold|