Malnutrition and Its Effect on Drug Pharmacokinetics: A Clinical Perspective.

Malnutrition significantly alters the pharmacokinetics of medications, particularly in vulnerable populations such as children, pregnant women, elderly individuals, and individuals in low- and middle-income countries. These populations are often more vulnerable to the effects of malnutrition because of physiological, metabolic and socioeconomic factors. Changes in body composition, organ function and plasma protein levels associated with malnutrition can impact drug absorption, distribution, metabolism and excretion. In malnourished individuals, decreased serum albumin levels may increase the free (unbound) fraction of highly protein-bound acidic drugs, potentially elevating the risk of toxicity. However, this relationship is not universally straightforward, as it depends on the drug's protein-binding characteristics, hepatic and renal function, volume of distribution and compensatory changes in drug clearance. In addition, malnutrition's effects on liver enzymes, such as cytochrome P450 isoforms, and kidney function can result in unpredictable drug clearance, particularly for narrow-therapeutic-index medications. Emerging evidence also highlights the interplay between malnutrition and pharmacogenomics, with genetic variations further modulating drug metabolism and response. Addressing these complexities requires the development of tailored dosing regimens and adaptive therapeutic strategies to optimise treatment outcomes in these at-risk groups. This review accentuates the critical need for more robust research to inform clinical guidelines and improve health equity in managing malnourished populations globally.