Alterations in drug disposition in older adults: a focus on geriatric syndromes

ABSTRACT

Introduction

Age-associated physiological changes can alter the disposition of drugs, however, pathophysiological changes associated with geriatric syndromes in older adults may lead to even greater heterogeneity in pharmacokinetics. Geriatric syndromes are common health problems in older adults which have multifactorial causes and do not fit into distinct organ-based disease categories. With older adults being the greatest users of medications, understanding both age- and geriatric syndrome-related changes is important clinically to ensure safe and effective medication use.

Areas covered

This review provides an overview of current evidence regarding pharmacokinetic alterations that occur with aging and in common geriatric syndromes, including frailty, sarcopenia, dementia, polypharmacy and enteral feeding. The evidence is presented according to the four primary pharmacokinetic processes (Absorption, Distribution, Metabolism and Excretion).

Expert opinion

There is some evidence to inform our understanding of the impact of chronological aging and various geriatric syndromes on drug disposition. However, many areas require more research, including drug induced inhibition and induction of cytochrome P450 enzymes and the clinical utility of emerging methods for estimating renal function. There is a need to develop tools to predict alterations in drug disposition in subgroups of older adults, particularly where the currently available clinical information is sparse.

KEYWORDS:

• Advancing age
• aging
• dementia
• drug disposition
• enteral feeding
• frailty
• geriatric syndromes
• pharmacokinetics
• polypharmacy
• sarcopenia

Article highlights

• The pharmacokinetics of drugs may be significantly different in older adults when compared to younger adults. Within the older patient population, drug pharmacokinetics might further differ according to the presence or absence of geriatric syndromes.

• Changes to oral drug absorption are unlikely to be clinically significant with ageing, although the evidence to support this is inconclusive. However, depending on the placement (pre or post pyloric), drugs administered via enteral feeding tubes may have significantly altered bioavailability.

• Significant changes in body weight, body composition (i.e. muscle mass and fat mass) and protein binding can occur with advanced age and in some geriatric syndromes including frailty and sarcopenia. Such changes can alter the volume of distribution of drugs.

• Drug clearance via hepatic metabolism and renal excretion is the most clinically significant pharmacokinetic parameter to guide drug dosing in older adults.

• In older adults there is reduced phase I metabolism in the liver due to reduced liver size, blood flow and oxygen supply. In frailty there may also be reduced phase II metabolism. Polypharmacy increases the risk of drug-drug interactions via hepatic enzymes.

• Older adults generally have reduced renal drug clearance compared to younger adults. Renal impairment is common in frail older adults due to their reduced capacity to recover post injury. Drug-drug interactions can also occur in the kidneys, affecting the clearance of drugs.

• This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.