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

This study has been completed.
Sponsor:
Collaborator:
The Hospital of Vestfold
Information provided by (Responsible Party):
University of Oslo School of Pharmacy
ClinicalTrials.gov Identifier:
NCT00331565
First received: May 29, 2006
Last updated: January 24, 2012
Last verified: January 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Morbid Obesity
 Procedure: Bariatric surgery
 Phase 4

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Oslo School of Pharmacy:

Primary Outcome Measures:
  • ratio of atorvastatin AUC0-8 between groups [ Time Frame: june 2009 ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ 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 ]

Enrollment: 36
Study Start Date: August 2006
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Bariatric surgery
    Gastric bypass, duodenal switch and sleeve surgery
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00331565

Locations
Norway
Hospital in Vestfold
Tønsberg, Norway, 3103
Sponsors and Collaborators
University of Oslo School of Pharmacy
The Hospital of Vestfold
Investigators
Principal Investigator: Rune Sandbu, MD, PhD Hospital in Vestfold
  More Information

No publications provided

Responsible Party: University of Oslo School of Pharmacy
ClinicalTrials.gov Identifier: NCT00331565     History of Changes
Other Study ID Numbers: ATORVA-06
Study First Received: May 29, 2006
Last Updated: January 24, 2012
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by University of Oslo School of Pharmacy:
Bariatric surgery
Bioavailability
Bioequivalence
Atorvastatin
 CYP's
P-gp
OATP

Additional relevant MeSH terms:
Obesity
Obesity, Morbid
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
 Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013