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Drug metabolism and ageing
1Department of Care of the Elderly, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK. Hilary.Wynne@nuth.northy.nhs.uk
The Journal of the British Menopause Society
|June 23, 2005
Summary
Older adults experience altered drug clearance due to age-related physiological changes, increasing adverse drug reaction risks. Starting medications at low doses and gradually increasing them is crucial for safe and effective treatment in the elderly.
Area of Science:
- Gerontology
- Clinical Pharmacology
- Pharmacokinetics
Background:
- Older adults are significant drug consumers, facing increased risks of adverse drug reactions due to co-morbidity and age-related physiological changes.
- Age-related reductions in hepatic drug clearance, specifically liver blood flow and size, significantly impact drug metabolism and elimination in older individuals.
Purpose of the Study:
- To elucidate the impact of aging on drug pharmacokinetics, focusing on hepatic drug clearance and its clinical implications.
- To provide guidance on safe medication management for older adults at risk of adverse drug reactions.
Main Methods:
- Review of age-related changes in drug absorption, distribution, protein binding, and hepatic clearance.
- Analysis of the effects of reduced liver blood flow and size on drug metabolism, including first-pass metabolism and capacity-limited pathways.
- Examination of factors influencing cytochrome P450 enzyme activity in aging populations.
Main Results:
- While drug absorption and distribution are not significantly altered by age, hepatic drug clearance is clinically important and reduced.
- Liver blood flow decreases by approximately 35% and liver size by 24-35% in older adults, affecting the clearance of various drugs.
- Cytochrome P450 enzyme activity is generally preserved in normal aging but can decline in frail individuals or those with co-morbidities.
Conclusions:
- Altered drug clearance in older adults necessitates careful medication management due to unpredictable interactions between age, co-morbidity, and drug therapy.
- Initiating drug therapy at low doses and titrating slowly, with close monitoring for efficacy and adverse effects, is a recommended strategy for elderly patients.