Official Title: “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 Type: Interventional

Study Design: Other, Non-Randomized, Open Label, Active Control, Parallel Assignment, Bio-equivalence Study

Study Primary Completion Date: June 2009

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.

Intervention(s) in this Clinical Trial

• Procedure: Bariatric surgery
  • Gastric bypass, duodenal switch and sleeve surgery

Primary Measures

• ratio of atorvastatin AUC0-8 between groups
  • Time Frame: june 2009
    Safety Issue?: No

Secondary Measures

• 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
    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
    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
    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
    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
    Safety Issue?: No
• Adverse events and serious adverse events will be listed.
  • Time Frame: june 2009
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Oslo School of Pharmacy

Overall Clinical Trial Officials and Contacts

Rune Sandbu, MD, PhD Principal Investigator Hospital in Vestfold  

Overall Contact: Anders Åsberg, Ph.D. +4722856559 anders.asberg@farmasi.uio.no

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00331565

Study ID Number: ATORVA-06

ClinicalTrials.gov Identifier: NCT00331565

Health Authority: Norway: Norwegian Medicines Agency