Document Detail

Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch.
MedLine Citation:
PMID:  20445535     Owner:  NLM     Status:  MEDLINE    
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.
I B Skottheim; G S Jakobsen; K Stormark; H Christensen; J Hjelmesaeth; T Jenssen; A Asberg; R Sandbu
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Publication Detail:
Type:  Clinical Trial; Journal Article     Date:  2010-05-05
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  87     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  699-705     Citation Subset:  AIM; IM    
School of Pharmacy, University of Oslo, Oslo, Norway.
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MeSH Terms
Area Under Curve
Biliopancreatic Diversion / methods*
Biological Availability
Dose-Response Relationship, Drug
Duodenum / surgery
Follow-Up Studies
Heptanoic Acids / administration & dosage,  pharmacokinetics*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage,  pharmacokinetics*
Intestine, Small / metabolism
Middle Aged
Obesity, Morbid / surgery*
Prospective Studies
Pyrroles / administration & dosage,  pharmacokinetics*
Reg. No./Substance:
0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 110862-48-1/atorvastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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