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- Title
Significant Increase in Systemic Exposure of Atorvastatin After Biliopancreatic Diversion With Duodenal Switch.
- Authors
Skottheim, I. B.; Jakobsen, G. S.; Stormark, K.; Christensen, H.; Hjelmesæth, J.; Jenssen, T.; Åsberg, A.; Sandbu, R.
- Abstract
Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure. Given that this procedure introduces a bypass of the proximal small intestine, it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability. Eight-hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at (median) 6 weeks (range, 4–8 weeks) in 10 morbidly obese patients who were receiving treatment with 20–80 mg atorvastatin each morning. The bioavailability of atorvastatin acid was significantly increased, with a mean twofold higher AUC0–8 after surgery (range 1.0–4.2, P = 0.001). Time to maximum plasma concentration (Cmax) increased from 1.2 h before surgery to 2.3 h after surgery (P = 0.03). The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds. Consequently, retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window.
- Subjects
SMALL intestine surgery; PHARMACOKINETICS; OVERWEIGHT persons; PATIENTS
- Publication
Clinical Pharmacology & Therapeutics, 2010, Vol 87, Issue 6, p699
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2010.32