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

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.

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.

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