Long-term effects of gastric bypass and duodenal switch on systemic exposure of atorvastatin

Surg Endosc. 2013 Jun;27(6):2094-101. doi: 10.1007/s00464-012-2716-3. Epub 2012 Dec 18.

Abstract

Background: A previous study of 22 patients undergoing either gastric bypass or duodenal switch showed increased systemic exposure of atorvastatin acid 3-8 weeks after surgery in the majority of patients. This study aimed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients.

Methods: An 8-h pharmacokinetic investigation was performed a median of 27 months (range 21-45 months) after surgery. Systemic exposure was measured as the area under the plasma concentration versus the time curve from 0 to 8 h postdose (AUC0-8). Linear mixed models with AUC0-8 as the dependent variable were implemented to assess the effect of time, surgical procedure, and body mass index (BMI) as explanatory variables.

Results: The study enrolled 20 patients. The systemic exposure of atorvastatin acid changed significantly over time (p = 0.001), albeit there was substantial variation between subjects. The effect of time was attenuated but remained significant after adjustment for surgical procedure and BMI (p = 0.048). The initial AUC0-8 increase seen in the majority of patients 3-8 weeks after surgery was normalized long term, with 7 of the 12 gastric bypass patients and 6 of the 8 duodenal switch patients showing decreased AUC0-8 compared with preoperative values.

Conclusions: The systemic exposure of atorvastatin showed a significant change over time after bariatric surgery, albeit with large inter- and intraindividual variations. The findings indicate that patients using atorvastatin or drugs with similar pharmacokinetic properties should be monitored closely for both therapeutic effects and adverse events the first years after gastric bypass and duodenal switch.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Atorvastatin
  • Biliopancreatic Diversion / adverse effects*
  • Biological Availability
  • Female
  • Gastric Bypass / adverse effects*
  • Heptanoic Acids / adverse effects
  • Heptanoic Acids / pharmacokinetics*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics*
  • Male
  • Middle Aged
  • Obesity, Morbid / surgery*
  • Prospective Studies
  • Pyrroles / adverse effects
  • Pyrroles / pharmacokinetics*

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin