13.5: Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Distribution

Drug distribution in the human body is influenced by several factors, including plasma protein concentration, body composition, blood flow, tissue-protein concentration, and tissue fluid pH. Among these, changes in plasma protein concentration and body composition due to aging significantly affect how drugs are distributed within the body. Specifically, aging is associated with a decrease in albumin levels by about 10% and an increase in α1-acid glycoprotein levels. These alterations are not directly caused by aging but rather by pathophysiological changes or diseases more common in older individuals. Consequently, these changes might not always necessitate adjustments in dosing regimens, except for drugs with a high extraction ratio and a narrow therapeutic index, such as intravenously administered lidocaine.

Furthermore, the process by which drugs bind to tissues and how this binding is affected by aging remains less understood, mainly due to the challenges of measuring tissue binding in vitro without compromising tissue integrity. As people age, there is a notable decrease in lean body mass and total body water, leading to a reduced distribution volume for hydrophilic drugs like digoxin, theophylline, and aminoglycosides. Conversely, an increase in body fat with age may increase the volume of distribution for lipophilic drugs, such as benzodiazepines, resulting in lower plasma drug concentrations for the same doses.

To achieve the same therapeutic drug concentration in older patients, it's essential to consider these changes in drug distribution. This often means adjusting single or loading doses of drugs, with a general recommendation for lower doses in older compared to younger patients. Implementing weight-based loading regimens can help tailor drug dosing more accurately to each individual's body composition changes with age, enhancing the safety and efficacy of pharmacotherapy in the elderly.

Aging affects drug distribution mainly through changes in plasma protein concentration and body composition.

Older individuals usually have decreased albumin levels and increased α1-acid glycoprotein levels.

As a result, drugs with narrow therapeutic indices, like lidocaine and highly protein-bound drugs like warfarin, require dosing regimen adjustments to reduce toxicity risks.

Aging also leads to decreased lean body mass and total body water. This reduces the distribution volume for hydrophilic drugs like digoxin, theophylline, and aminoglycosides.

Conversely, body fat increases with age. This can potentially increase the volume of distribution for lipophilic drugs like benzodiazepines, resulting in lower plasma drug concentrations for equivalent doses.