Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin

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-depen...

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Autores principales:	Arik Dahan, Daniel Porat, Milica Markovic, Moran Zur, Olga Kister, Peter Langguth
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bariatric surgery Roux-en-Y gastric bypass obesity metformin GastroPlus<sup>TM</sup> intestinal permeability Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/8ebf2fb240e84f12ad8b7c8d56b0e37c
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spelling	oai:doaj.org-article:8ebf2fb240e84f12ad8b7c8d56b0e37c2021-11-25T18:41:20ZOptimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin10.3390/pharmaceutics131118731999-4923https://doaj.org/article/8ebf2fb240e84f12ad8b7c8d56b0e37c2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1873https://doaj.org/toc/1999-4923Bariatric 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 GastroPlus<sup>TM</sup> 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<sup>TM</sup> 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.Arik DahanDaniel PoratMilica MarkovicMoran ZurOlga KisterPeter LangguthMDPI AGarticlebariatric surgeryRoux-en-Y gastric bypassobesitymetforminGastroPlus<sup>TM</sup>intestinal permeabilityPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1873, p 1873 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bariatric surgery Roux-en-Y gastric bypass obesity metformin GastroPlus<sup>TM</sup> intestinal permeability Pharmacy and materia medica RS1-441
spellingShingle	bariatric surgery Roux-en-Y gastric bypass obesity metformin GastroPlus<sup>TM</sup> intestinal permeability Pharmacy and materia medica RS1-441 Arik Dahan Daniel Porat Milica Markovic Moran Zur Olga Kister Peter Langguth Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
description	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 GastroPlus<sup>TM</sup> 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<sup>TM</sup> 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.
format	article
author	Arik Dahan Daniel Porat Milica Markovic Moran Zur Olga Kister Peter Langguth
author_facet	Arik Dahan Daniel Porat Milica Markovic Moran Zur Olga Kister Peter Langguth
author_sort	Arik Dahan
title	Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
title_short	Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
title_full	Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
title_fullStr	Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
title_full_unstemmed	Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
title_sort	optimized in silico modeling of drug absorption after gastric bypass: the case of metformin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8ebf2fb240e84f12ad8b7c8d56b0e37c
work_keys_str_mv	AT arikdahan optimizedinsilicomodelingofdrugabsorptionaftergastricbypassthecaseofmetformin AT danielporat optimizedinsilicomodelingofdrugabsorptionaftergastricbypassthecaseofmetformin AT milicamarkovic optimizedinsilicomodelingofdrugabsorptionaftergastricbypassthecaseofmetformin AT moranzur optimizedinsilicomodelingofdrugabsorptionaftergastricbypassthecaseofmetformin AT olgakister optimizedinsilicomodelingofdrugabsorptionaftergastricbypassthecaseofmetformin AT peterlangguth optimizedinsilicomodelingofdrugabsorptionaftergastricbypassthecaseofmetformin
_version_	1718410786682961920

Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin

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