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...
Date First Received: May 29, 2006
Last Updated: June 9, 2008
Verified by: University of Oslo School of Pharmacy, June 2008
Clinical Trial Phase: Phase 4 | Start Date: August 2006
Overall Status: Recruiting
Estimated Enrollment: 24
Brief Summary
Official Title: “Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin”
Condition Keyword(s):
Intervention(s):
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: December 2008
Detailed Clinical Trial 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.
Intervention(s) in this Clinical Trial
- Procedure: Bariatric surgery
Outcome Measures for this Clinical Trial
Primary Measures
- ratio of atorvastatin AUC0-8 between groups
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%.
- Descriptive comparison of mRNA expression of CYP3A4, CYP3A5, P-gp and OATP1B1 in different biopsies and atorvastatin and metabolites pharmacokinetics.
- Descriptive comparison of protein expression of CYP3A4, CYP3A5 and P-gp in different biopsies and atorvastatin and its metabolites pharmacokinetics.
- 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.
- Descriptive listing of the relationship between plasma and skeletal muscle as well as adipose tissue concentrations of atorvastatin and metabolites.
- Adverse events and serious adverse events will be listed.
Criteria for Participation in this Clinical Trial
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
Clinical Trial Sponsor Information
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
Additional Information
Information obtained from ClinicalTrials.gov on September 05, 2008
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
Clinical Trials Authorship and Review
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