Drug Metabolism in Older People--A Key Consideration in Achieving Optimal Outcomes With Medicines

Abstract

Hepatic clearance plays a key role in determining the systemic exposure of drugs and metabolites, which in turn has a major effect on variability in the beneficial and adverse effects of medicines. Aging results in a number of significant changes in the human liver including reductions in liver blood flow, size, drug-metabolizing enzyme content, and pseudocapillarization. Drug metabolism is also influenced by comorbid disease, frailty, concomitant medicines, and (epi)genetics. These changes have the potential to alter the hepatic clearance of drugs but need to be interpreted in the context of the pharmacokinetic (and pharmacodynamic) characteristics of the drug of interest. There is growing evidence that the age-related changes in the liver not only result in a decrease in the hepatic clearance of unbound drug but also influence variability in response to medicines in older people.

Utility of non-human primates in drug development: Comparison of non-human primate and human drug-metabolizing cytochrome P450 enzymes

“…The age-related alterations of pharmacokinetics have been well summarized in humans [34][35][36]. During drug development, it is important to predict how the pharmacokinetics of drug candidates will change in older patients to reduce related risks.…”

Strategies to Improve Medication Adherence in Older Persons: Consensus Statement from the Senior Italia Federanziani Advisory Board

“…Figure 1 provides a summary of the major factors influencing individualised dose selection in older people to achieve optimal health outcomes from antifungal treatment [11][12][13][14]. While a person's numerical age is a poor guide to dosing, most patients are considered in the 'elderly' cohort at the age of 65 years and above.…”

“…Here, extrinsic factors, such as changes in clearance due to the impact of the ageing liver and kidney and drug-drug interactions due to polypharmacy, have a greater impact on the pharmacokinetics of antifungal drugs [11][12][13][14][15][16]. Frailty has been identified as a major factor contributing to pharmacokinetic variability [13,17], including for some antimicrobial agents [18].…”

Medication-Related Factors Affecting Discharge to Home

“…18,19) Age-related pharmacodynamic and pharmacokinetic changes increase the susceptibility of elderly patients to adverse reactions from medications. [20][21][22] In Japan, pharmaceutical counseling at discharge is not common, which could be a reason why no factors in drug-related items were identified as determinants of home discharge in this study. Performing an accurate medication reconciliation is a critical element of a successful discharge transition.…”