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

NCT00331565 | Completed Phase 4

• 1 other identifier: ATORVA-06
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Morbid Obesity

Keywords

Bariatric surgery; Bioavailability; Bioequivalence; Atorvastatin; CYP's; P-gp; OATP

Outcome Measures

Primary Outcomes (1)

• ratio of atorvastatin AUC0-8 between groups

  june 2009

Secondary Outcomes (6)

• 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 mRNA expression of CYP3A4, CYP3A5, P-gp and OATP1B1 in different biopsies and atorvastatin and metabolites pharmacokinetics.

  june 2009

• Descriptive comparison of protein expression of CYP3A4, CYP3A5 and P-gp in different biopsies and atorvastatin and its metabolites pharmacokinetics.

  december 2009

• 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

Study Arms (1)

Surgery

EXPERIMENTAL

Bariatric surgery

Procedure: Bariatric surgery

Interventions

Bariatric surgery PROCEDURE

Gastric bypass, duodenal switch and sleeve surgery

Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Scheduled for bariatric surgery.
• years of age or older.
• Ongoing treatment with statin.
• Able and willing to donate GI-tract and liver biopsies.
• Signed informed consent.

You may not qualify if:

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

Sponsors & Collaborators

• University of Oslo School of Pharmacy: lead
• The Hospital of Vestfold: collaborator

Study Sites (1)

Hospital in Vestfold

Tønsberg, 3103, Norway

Location

MeSH Terms

Conditions

Obesity, Morbid

Interventions

Bariatric Surgery

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative

Study Officials

• Rune Sandbu, MD, PhD

  Hospital in Vestfold

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2006
• First Posted: May 31, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 3, 2014

Record last verified: 2014-12

Locations

NO (1)