Impact of Gastrointestinal Disease States on Oral Drug Absorption – implications for formulation design – a PEARRL review

Angela Effinger, Caitriona M. O'Driscoll, Mark McAllister, Nikoletta Fotaki

Research output: Contribution to journalReview article

12 Citations (Scopus)
28 Downloads (Pure)

Abstract

Objectives: Drug product performance in patients with gastrointestinal (GI) diseases can be altered compared to healthy subjects due to pathophysiological changes. In this 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. Key findings: Drug product performance was altered in patients with GI diseases compared to healthy subjects, as assessed in a limited number of studies for some drugs. Underlying causes can be observed pathophysiological alterations such as the differences in GI transit time, the composition of the GI fluids and GI permeability. Additionally, alterations in the abundance of metabolising enzymes and transporter systems were observed. The effect of the GI diseases on each parameter is not always evident as it may depend on the location and the state of the disease. The impact of the pathophysiological change on drug bioavailability depends on the physicochemical characteristics of the drug, the pharmaceutical formulation and drug metabolism. In vitro and in silico methods to predict drug product performance in patients with GI diseases are currently limited but could be a useful tool to improve drug therapy. Summary: Development of suitable in vitro dissolution and in silico models for patients with GI diseases can improve their drug therapy. The likeliness of the models to provide accurate predictions depends on the knowledge of pathophysiological alterations, and thus, further assessment of physiological differences is essential.

Original languageEnglish
Pages (from-to)674-698
Number of pages25
JournalJournal of Pharmacy and Pharmacology
Volume71
Issue number4
Early online date16 May 2018
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • formulation
  • gastrointestinal diseases
  • gastrointestinal physiology
  • in vitro and PBPK models
  • oral drug absorption

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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