Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications Advancing age is associated with physiological changes that affect drug metabolism and response. These changes include reduced renal and hepatic clearance, increased volume of distribution for lipid-soluble drugs, and altered sensitivity to various drug classes. The review discusses the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs. Age-related changes in the cardiovascular system include reduced elasticity and compliance of the aorta and great arteries, leading to increased systolic arterial pressure and left ventricular hypertrophy. The heart rate decreases, and the response to postural changes differs between young and elderly subjects. During exercise, the tachycardic response is reduced, and cardiac output may be maintained through increased stroke volume. The renal system undergoes changes with age, including reduced renal mass and glomerular filtration rate. Creatinine is not a reliable indicator of glomerular filtration rate in the elderly. The ability to concentrate urine is reduced, and the response to water loading is impaired. The gastrointestinal system shows changes in gastric acid secretion and absorption. The small intestine experiences reduced absorption of certain substances, while digestion and motility remain relatively unchanged. The colon exhibits conflicting results regarding age-related changes in motility. The liver undergoes age-related changes, including reduced liver volume and blood flow. However, liver function tests do not show significant differences between individuals aged 50–69 and 70–89 years. Neuroendocrine responses are affected by age, with changes in the hypothalamic-pituitary-adrenal (HPA) axis. Age-related changes in body composition, including reduced total body water and lean body mass, contribute to increased body fat. Pharmacokinetic changes with age include reduced gastric acid secretion, gastric emptying, and absorptive capacity of the small intestine. However, more recent studies in healthy subjects have not confirmed these findings. First-pass metabolism is reduced, leading to increased bioavailability of drugs undergoing extensive first-pass metabolism. Drug distribution is affected by changes in body composition, with water-soluble drugs having smaller volumes of distribution and lipid-soluble drugs having increased volumes of distribution. Pharmacodynamic changes with age include increased sensitivity to drugs such as anticoagulants, cardiovascular drugs, and psychotropic drugs. Age-related changes in drug sensitivity are influenced by changes in body composition, hepatic and renal function, and the ability to maintain homeostasis. The review concludes that the ageing process is characterized by structural and functional changes affecting all organ systems, leading to reduced homeostatic capacity. These changes increase vulnerability to stress and affect drug metabolism and response. Understanding the effects of ageing on clinical pharmacology is essential for effective prescribing.Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications Advancing age is associated with physiological changes that affect drug metabolism and response. These changes include reduced renal and hepatic clearance, increased volume of distribution for lipid-soluble drugs, and altered sensitivity to various drug classes. The review discusses the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs. Age-related changes in the cardiovascular system include reduced elasticity and compliance of the aorta and great arteries, leading to increased systolic arterial pressure and left ventricular hypertrophy. The heart rate decreases, and the response to postural changes differs between young and elderly subjects. During exercise, the tachycardic response is reduced, and cardiac output may be maintained through increased stroke volume. The renal system undergoes changes with age, including reduced renal mass and glomerular filtration rate. Creatinine is not a reliable indicator of glomerular filtration rate in the elderly. The ability to concentrate urine is reduced, and the response to water loading is impaired. The gastrointestinal system shows changes in gastric acid secretion and absorption. The small intestine experiences reduced absorption of certain substances, while digestion and motility remain relatively unchanged. The colon exhibits conflicting results regarding age-related changes in motility. The liver undergoes age-related changes, including reduced liver volume and blood flow. However, liver function tests do not show significant differences between individuals aged 50–69 and 70–89 years. Neuroendocrine responses are affected by age, with changes in the hypothalamic-pituitary-adrenal (HPA) axis. Age-related changes in body composition, including reduced total body water and lean body mass, contribute to increased body fat. Pharmacokinetic changes with age include reduced gastric acid secretion, gastric emptying, and absorptive capacity of the small intestine. However, more recent studies in healthy subjects have not confirmed these findings. First-pass metabolism is reduced, leading to increased bioavailability of drugs undergoing extensive first-pass metabolism. Drug distribution is affected by changes in body composition, with water-soluble drugs having smaller volumes of distribution and lipid-soluble drugs having increased volumes of distribution. Pharmacodynamic changes with age include increased sensitivity to drugs such as anticoagulants, cardiovascular drugs, and psychotropic drugs. Age-related changes in drug sensitivity are influenced by changes in body composition, hepatic and renal function, and the ability to maintain homeostasis. The review concludes that the ageing process is characterized by structural and functional changes affecting all organ systems, leading to reduced homeostatic capacity. These changes increase vulnerability to stress and affect drug metabolism and response. Understanding the effects of ageing on clinical pharmacology is essential for effective prescribing.