title: Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch.
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 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.
authors.affiliation: School of Pharmacy, University of Oslo, Oslo, Norway.
authors.forename: I B
authors.initials: IB
authors.lastname: Skottheim
authors.forename: G S
authors.initials: GS
authors.lastname: Jakobsen
authors.forename: K
authors.initials: K
authors.lastname: Stormark
authors.forename: H
authors.initials: H
authors.lastname: Christensen
authors.forename: J
authors.initials: J
authors.lastname: Hjelmesaeth
authors.forename: T
authors.initials: T
authors.lastname: Jenssen
authors.forename: A
authors.initials: A
authors.lastname: Asberg
authors.forename: R
authors.initials: R
authors.lastname: Sandbu
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D000069059:Atorvastatin; D015904:Biliopancreatic Diversion / Q000379:methods*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000601:surgery*; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin