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 region-dependent permeability of metformin, using the rat single-pass intestinal perfusion method (SPIP), which we then implemented into GastroPlusTM 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, GastroPlusTM 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.
Highlights
Since the 1980s the prevalence of obesity has more than doubled, and is a global epidemic
Obesity is related to many comorbidities, including type 2 diabetes, hypertension, dyslipidemia, and sleep apnea [1], as well as unfortunate outcomes that lead to a shorter life expectancy [2]
Ultra-performance liquid chromatography (UPLC) was performed on a Waters (Milford, MA, USA) Acquity UPLC H-Class system equipped with a photodiode array detector (PDA) and Empower software
Summary
Since the 1980s the prevalence of obesity has more than doubled, and is a global epidemic. Obesity is related to many comorbidities, including type 2 diabetes, hypertension, dyslipidemia, and sleep apnea [1], as well as unfortunate outcomes that lead to a shorter life expectancy [2]. Since diet and exercise alone cannot quite achieve the desired weight loss, there is a need for other, long-term, effective treatments for obesity. For patients with severe obesity (BMI > 40), there are currently few therapies or pharmaceuticals offering lasting weight loss. In these cases, bariatric surgery is suggested [3]. There are several available bariatric surgical techniques, with Roux-en-Y gastric bypass (RYGB) long being the gold standard [4]. The operation results in a smaller gastric pouch to restrict oral intake and the construction of an intestinal limb where bile and pancreatic fluid are diverted from the proximal to distal intestine (Figure 1) to limit food absorption
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call