Altered peripheral factors affecting the absorption, distribution, metabolism, and excretion of oral medicines in Alzheimer's disease

Adv Drug Deliv Rev. 2022 Jun;185:114282. doi: 10.1016/j.addr.2022.114282. Epub 2022 Apr 11.

Abstract

Alzheimer's disease (AD) has traditionally been considered solely a neurological condition. Therefore, numerous studies have been conducted to identify the existence of pathophysiological changes affecting the brain and the blood-brain barrier in individuals with AD. Such studies have provided invaluable insight into possible changes to the central nervous system exposure of drugs prescribed to individuals with AD. However, there is now increasing recognition that extra-neurological systems may also be affected in AD, such as the small intestine, liver, and kidneys. Examination of these peripheral pathophysiological changes is now a burgeoning area of scientific research, owing to the potential impact of these changes on the absorption, distribution, metabolism, and excretion (ADME) of drugs used for both AD and other concomitant conditions in this population. The purpose of this review is to identify and summarise available literature reporting alterations to key organs influencing the pharmacokinetics of drugs, with any changes to the small intestine, liver, kidney, and circulatory system on the ADME of drugs described. By assessing studies in both rodent models of AD and samples from humans with AD, this review highlights possible dosage adjustment requirements for both AD and non-AD drugs so as to ensure the achievement of optimum pharmacotherapy in individuals with AD.

Keywords: Absorption; Alzheimer’s disease; Distribution; Excretion; Metabolising enzymes; Metabolism; Pharmacokinetics; Transporters.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Biological Transport
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Humans
  • Intestine, Small / metabolism