A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution

@article{Darwich2012AMP,
  title={A mechanistic pharmacokinetic model to assess modified oral drug bioavailability post bariatric surgery in morbidly obese patients: interplay between CYP3A gut wall metabolism, permeability and dissolution},
  author={Adam S. Darwich and Devendra Pade and Basil J. Ammori and Masoud Jamei and Darren M. Ashcroft and Amin Rostami-Hodjegan},
  journal={Journal of Pharmacy and Pharmacology},
  year={2012},
  volume={64}
}
Objectives  Due to the multi‐factorial physiological implications of bariatric surgery, attempts to explain trends in oral bioavailability following bariatric surgery using singular attributes of drugs or simplified categorisations such as the biopharmaceutics classification system have been unsuccessful. So we have attempted to use mechanistic models to assess changes to bioavailability of model drugs. 

Evaluation of an In Silico PBPK Post-Bariatric Surgery Model through Simulating Oral Drug Bioavailability of Atorvastatin and Cyclosporine

Simulated atorvastatin Foral postsurgery was broadly reflective of observed data with indications of counteracting interplay between reduced fa and an increased fraction escaping gut wall metabolism, highlighting the current gap regarding the knowledge of associated biological changes.

The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

Predicting the pharmacokinetic change for a specific drug following RYGBP is challenging and close monitoring of each individual drug is recommended in the early postsurgical phase, as the majority of available data is based on Roux‐en‐Y gastric bypass.

Physiologically-based pharmacokinetic modelling and simulation of oral drug bioavailability: Focus on bariatric surgery patients and mechanism-based inhibition of gut wall metabolism

The aim of this thesis was to explore the interplay between oral drug absorption and metabolism occurring in the GI tract through the exploration of the impact of bariatric surgery on oral drug exposure and by theoretically examining the nesting and hierarchy of enterocyte and enzyme turnover and its impact on MBIs in the small intestine.

Impact of gastrointestinal disease states on oral drug absorption – implications for formulation design – a PEARRL review

relevant differences in patients with inflammatory bowel diseases, coeliac disease, irritable bowel syndrome and short bowel syndrome are discussed and possible in vitro and in silico tools to predict drug product performance in this patient population are assessed.

Managing the Unpredictable: Mechanistic Analysis and Clinical Recommendations for Lamotrigine Treatment after Bariatric Surgery

A thorough mechanistic analysis of the effects of bariatric surgery on multiple mechanisms important for the absorption, bioavailability and overall pharmacokinetics of lamotrigine is provided, aiming to allow better patient care, and emphasizing the extra caution that needs to be taken with these patients.

RYGB and Drug Disposition: How to Do Better? Analysis of Pharmacokinetic Studies and Recommendations for Clinical Practice

All pharmacokinetic studies involving at least four subjects who underwent the Roux-en-Y gastric bypass (RYGB) bariatric surgery were reviewed and a strategy aiming to guide prescription and drug monitoring in patients with RYGB was proposed.

Physiologically-Based Pharmacokinetic Model on the Oral Drug Absorption in Roux-en-Y Gastric Bypass Bariatric Patients: Amoxicillin Tablet and Suspension

The PBPK model showed a reduction in AMX bioavailability as a consequence of reduced intestinal length after RYGB surgery, and the difference in the predicted Fd and Fabs between suspension and tablet suggests that liquid formulations are preferable in postbariatric patients.

Impact of Roux-en-Y Gastric Bypass Surgery on Pharmacokinetics of Administered Drugs: Implications and Perspectives

  • N. Srinivas
  • Medicine, Biology
    American journal of therapeutics
  • 2016
Based on the review, there is a significant risk of therapy failure for certain drugs because of subtherapeutic plasma levels and the need to readjust doses immediately after RYGB may be considered based on the therapeutic drug monitoring (TDM) findings.

Effect of Roux‐en‐Y gastric bypass on the pharmacokinetic‐pharmacodynamic relationships of liquid and controlled‐release formulations of oxycodone

Generic substitution of monophasic lipid-based and water-swellable controlled-release oxycodone tablets may be considered safe in RYGB patients.

The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery

In this cohort study in morbidly obese patients, systemic clearance was 1.7 times higher 1 year after bariatric surgery, which may potentially result from an increase in hepatic CYP3A activity per unit of liver weight.
...

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