Optimized in silico modeling of drug absorption after gastric bypass: The case of metformin

Arik Dahan, Daniel Porat, Milica Markovic, Moran Zur, Olga Kister, Peter Langguth

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Bariatric surgery is an effective treatment for severe obesity and related comorbidities, such as type II diabetes. Gastric bypass surgery shortens the length of the intestine, possibly leading to altered drug absorption. Metformin, a first-line treatment for type II diabetes, has permeability-dependent drug absorption, which may be sensitive to intestinal anatomic changes during bypass surgery, including Roux-en-Y gastric bypass (RYGB). Previous computer simulation data indicate increased metformin absorption after RYGB. In this study, we experimentally determined the re-gion-dependent permeability of metformin, using the rat single-pass intestinal perfusion method (SPIP), which we then implemented into GastroPlus™ to assess the contribution of our SPIP data to post-RYGB metformin absorption modeling. Previous simulations allowed a good fit with in vivo literature data on healthy and obese control subjects. However, it was revealed that for post-RYGB drug absorption predictions, simply excluding the duodenum/jejunum is insufficient, as the software underestimates the observed plasma concentrations post-RYGB. By implementing experimentally determined segmental-dependent permeabilities for metformin in the remaining segments post-surgery, GastroPlus™ proved to fit the observed plasma concentration profile, making it a useful tool for predicting drug absorption after gastric bypass. Reliable evaluation of the parameters dictating drug absorption is required for the accurate prediction of overall absorption after bariatric surgery.

Original languageEnglish
Article number1873
JournalPharmaceutics
Volume13
Issue number11
DOIs
StatePublished - 1 Nov 2021

Keywords

  • Bariatric surgery
  • GastroPlus™
  • Intestinal permeability
  • Metformin
  • Obesity
  • Program simulation
  • Roux-en-Y gastric bypass
  • Segmental-dependent absorption

ASJC Scopus subject areas

  • Pharmaceutical Science

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