Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption

Mirko Koziolek, Frédéric Carrière, Christopher J.H. Porter

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to ‘pre-process’ lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.

Original languageEnglish
Article number55
Number of pages26
JournalPharmaceutical Research
Volume35
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Biorelevant dissolution
  • Food effect
  • Gastric lipolysis
  • Human gastric lipase
  • In vitro digestion
  • Lipids
  • Milk

Cite this

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abstract = "Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to ‘pre-process’ lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.",
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Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption. / Koziolek, Mirko; Carrière, Frédéric; Porter, Christopher J.H.

In: Pharmaceutical Research, Vol. 35, No. 3, 55, 01.03.2018.

Research output: Contribution to journalReview ArticleResearchpeer-review

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