Barry J Cusack1. 1. Gerontology and Pharmacology Research Unit, VA Medical Center, Boise, Idaho 83702, USA. barry.cusack@med.va.gov
Abstract
BACKGROUND: Physiologic changes and disease-related alterations in organ function occur with aging. These changes can affect drug pharmacokinetics in older persons. OBJECTIVE: This article reviews age-related changes in pharmacokinetics and their clinical relevance. METHODS: A PubMed search was conducted using the terms elderly and pharmacokinetics. Other reviews were also included for literature searching. The review includes literature in particular from 1990 through April 2004. Some articles from before 1990 were included to help illustrate principles of age-related pharmacokinetics. RESULTS: There are minor changes in drug absorption with aging. The effect of aging on small-bowel transporter systems is not yet fully established. Bioavailability of highly extracted drugs often is increased with age. Transdermal absorption may be delayed, especially in the case of water-soluble compounds. Fat-soluble drugs may distribute more widely and water-soluble drugs less extensively in older persons. Hepatic drug metabolism shows wide interindividual variation, and in many cases, there is an age-related decline in elimination of metabolized drugs, particularly those eliminated by the cytochrome enzyme system. Any decrement in cytochrome enzyme metabolism appears nonselective. Synthetic conjugation metabolism is less affected by age. Pseudocapillarization of the sinusoidal endothelium in the liver, restricting oxygen diffusion, and the decline in liver size and liver blood flow may influence age-related changes in rate of hepatic metabolism. Frailty, physiological stress, and illness are important predictors of drug metabolism in older individuals. Inhibition of drug metabolism is not altered with aging, but induction is reduced in a minority of studies. Renal drug elimination typically declines with age, commensurate with the fall in creatinine clearance. Renal tubular organic acid transport may decline with age, while the function of the organic base transporter is preserved but may be less responsive to stimulation. CONCLUSION: Changes in pharmacokinetics occur due to age-related physiologic perturbations. These changes contribute to altered dose requirements in older persons, particularly in the case of drugs eliminated by the kidney. Interindividual variation, disease, frailty, and stress may overshadow age-related changes.
BACKGROUND: Physiologic changes and disease-related alterations in organ function occur with aging. These changes can affect drug pharmacokinetics in older persons. OBJECTIVE: This article reviews age-related changes in pharmacokinetics and their clinical relevance. METHODS: A PubMed search was conducted using the terms elderly and pharmacokinetics. Other reviews were also included for literature searching. The review includes literature in particular from 1990 through April 2004. Some articles from before 1990 were included to help illustrate principles of age-related pharmacokinetics. RESULTS: There are minor changes in drug absorption with aging. The effect of aging on small-bowel transporter systems is not yet fully established. Bioavailability of highly extracted drugs often is increased with age. Transdermal absorption may be delayed, especially in the case of water-soluble compounds. Fat-soluble drugs may distribute more widely and water-soluble drugs less extensively in older persons. Hepatic drug metabolism shows wide interindividual variation, and in many cases, there is an age-related decline in elimination of metabolized drugs, particularly those eliminated by the cytochrome enzyme system. Any decrement in cytochrome enzyme metabolism appears nonselective. Synthetic conjugation metabolism is less affected by age. Pseudocapillarization of the sinusoidal endothelium in the liver, restricting oxygen diffusion, and the decline in liver size and liver blood flow may influence age-related changes in rate of hepatic metabolism. Frailty, physiological stress, and illness are important predictors of drug metabolism in older individuals. Inhibition of drug metabolism is not altered with aging, but induction is reduced in a minority of studies. Renal drug elimination typically declines with age, commensurate with the fall in creatinine clearance. Renal tubular organic acid transport may decline with age, while the function of the organic base transporter is preserved but may be less responsive to stimulation. CONCLUSION: Changes in pharmacokinetics occur due to age-related physiologic perturbations. These changes contribute to altered dose requirements in older persons, particularly in the case of drugs eliminated by the kidney. Interindividual variation, disease, frailty, and stress may overshadow age-related changes.
Authors: Andrew J McLachlan; Sally Bath; Vasi Naganathan; Sarah N Hilmer; David G Le Couteur; Stephen J Gibson; Fiona M Blyth Journal: Br J Clin Pharmacol Date: 2011-03 Impact factor: 4.335
Authors: Lauren W Roth; Erica L Bradshaw-Pierce; Amanda A Allshouse; Jennifer Lesh; Justin Chosich; Andrew P Bradford; Alex J Polotsky; Nanette Santoro Journal: J Clin Endocrinol Metab Date: 2014-03-20 Impact factor: 5.958