Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin

Phase 4

Completed

• Conditions: Morbid Obesity

• Registration Number: NCT00331565
• Lead Sponsor: University of Oslo School of Pharmacy

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2006-05-29
• Study First Submitted QC: 2006-05-29
• Study First Posted: 2006-05-31
• Study Start: 2006-08
• Primary Completion: 2010-12
• Study Completion: 2010-12
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-02
• Last Update Posted: 2014-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• 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.

Exclusion Criteria

• Concomitant treatment with drugs and/or other factors that may influence atorvastatin pharmacokinetics

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
ratio of atorvastatin AUC0-8 between groups	june 2009

Secondary Outcome Measures

Name	Time	Method
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
Descriptive comparison of mRNA expression of CYP3A4, CYP3A5, P-gp and OATP1B1 in different biopsies and atorvastatin and metabolites pharmacokinetics.	june 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

Trial Locations

Locations (1)

Hospital in Vestfold; 🇳🇴 Tønsberg, Norway