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Significant Increase in Systemic Exposure of Atorvastatin After Biliopancreatic Diversion With Duodenal Switch
Author(s) -
Skottheim I B,
Jakobsen G S,
Stormark K,
Christensen H,
Hjelmesæth J,
Jenssen T,
Åsberg A,
Sandbu R
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.32
Subject(s) - biliopancreatic diversion , bioavailability , duodenal switch , medicine , pharmacokinetics , atorvastatin , duodenum , small intestine , gastroenterology , surgery , urology , weight loss , pharmacology , gastric bypass , obesity
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 AUC 0–8 after surgery (range 1.0–4.2, P = 0.001). Time to maximum plasma concentration ( C max ) 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. Clinical Pharmacology & Therapeutics (2010) 87 6, 699–705. doi: 10.1038/clpt.2010.32