Pharmacokinetic Implications of Pathophysiological Changes in Cachexia Syndrome: A Scoping Review.

Abstract

Introduction: Cachexia is a complex multi-organ syndrome characterized by systemic alterations that could impact drug pharmacokinetics. This scoping review aims to examine and synthesize existing research on the pathophysiological changes in cachexia that may influence drug pharmacokinetics.

Methods: A comprehensive literature search was conducted across five databases from inception to December 2024. Study selection was refined using the population, concept, and context (PCC) framework. The population included humans and animals with cachexia, the concept focused on cachexia-induced pathophysiological changes in relation to drug pharmacokinetics, and the context encompassed any clinical, healthcare setting, or laboratory settings.

Results: Out of 2684 identified studies, 53 met the inclusion criteria: 25 were based on human data, 18 on animal data, and 10 were reviews. The findings suggest that cachexia may impair drug absorption due to reduced skinfold thickness, gut dysbiosis, and structural and functional alterations in the gastrointestinal (GI) tract. Similarly, drug distribution may also be affected by changes in body composition and decreased serum albumin levels.

Conclusions: Pathophysiological changes in cachexia may lead to alterations in drug absorption and distribution, contributing to variability in drug bioavailability. However, the lack of controlled clinical trials directly linking cachexia-induced physiological changes to specific drug pharmacokinetics renders these findings tentative.