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Factors Affecting Drug Biotransformation: Biological

Factors Affecting Drug Biotransformation: Biological

Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
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Drug Dosing: Geriatric Patients

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Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...

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As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...

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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...

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism

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Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...

Pharmacodynamics in Geriatric Patients: Effects of Age

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Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...

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Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans

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Drug metabolism and ageing.

M T Kinirons¹, M S O'Mahony

¹Department of Health Care of the Elderly, Guy's, King's, and St Thomas' School of Medicine, King's College London, London, UK. mark.kinirons@gstt.sthames.nhs.uk

British Journal of Clinical Pharmacology

|April 20, 2004

Summary

Drug metabolism significantly changes with aging, affecting cytochrome P450 enzymes and transporters. Frail older individuals exhibit altered drug disposition compared to healthy elderly or young adults.

Area of Science:

Pharmacology
Gerontology
Drug Metabolism

Background:

Aging is associated with significant alterations in drug metabolism.
Reductions in cytochrome P450 enzyme (CYP) function are observed in some, but not all, individuals.
The impact of aging on drug transporters remains largely unexamined.

Purpose of the Study:

To revisit the induction and inhibition of CYPs considering recent advancements.
To investigate age-related effects on the function and pharmacology of drug transporters.
To explore the relationship between frailty and drug metabolism/disposition in older adults.

Main Methods:

Review of recent advances in CYP enzyme research.
Examination of age-related changes in drug transporter function.

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Comparative analysis of drug metabolism and disposition in frail elderly, healthy elderly, and young individuals.

Main Results:

Age-associated functional declines in certain CYPs are documented.
Frailty in older adults is linked to reduced drug metabolism and altered drug disposition.
Significant knowledge gaps exist regarding age-related transporter pharmacology.

Conclusions:

Aging profoundly impacts drug metabolism, affecting both CYPs and transporters.
Frailty represents a critical factor influencing drug disposition in the elderly.
Further research is needed to fully elucidate age-related changes in drug disposition and inform clinical practice.