Morbid Obesity
Conditions
Keywords
Bariatric surgery, Bioavailability, Bioequivalence, Atorvastatin, CYP's, P-gp, OATP
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.
Interventions
PROCEDUREBariatric surgery
Gastric bypass, duodenal switch and sleeve surgery
Sponsors
The Hospital of Vestfold
University of Oslo School of Pharmacy
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ratio of atorvastatin AUC0-8 between groups | june 2009 |
Secondary
| Measure | Time frame |
|---|---|
| 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 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 |
| Adverse events and serious adverse events will be listed. | june 2009 |
| Descriptive comparison of protein expression of CYP3A4, CYP3A5 and P-gp in different biopsies and atorvastatin and its metabolites pharmacokinetics. | december 2009 |
Countries
Norway
Outcome results
None listed