Age-related changes in pharmacokinetics.

Abstract:

:Ageing is characterized by a progressive decline in the functional reserve of multiple organs and systems, which can influence drug disposition. In addition, comorbidity and polypharmacy are highly prevalent in the elderly. As ageing is associated with some reduction in first-pass metabolism, bioavailability of a few drugs can be increased. With ageing body fat increases and total body water as well as lean body mass decrease. Consequently, hydrophilic drugs have a smaller apparent volume of distribution (V) and lipophilic drugs have an increased V with a prolonged half-life. Drugs with a high hepatic extraction ratio display some age-related decrease in systemic clearance (CL), but for most drugs with a low hepatic extraction ratio, CL is not reduced with advancing age. In general, activities of cytochrome P450 enzymes are preserved in normal ageing and the genetic influence is much more striking than age effects. Drug transporters play an important role in pharmacokinetic processes, but their function and pharmacology have not yet been fully examined for agerelated effects. One third of elderly persons show no decrease in renal function (GFR > 70 mL/min/1.73 m2). In about two thirds of elderly subjects, the age-related decline of renal function was associated with coexisting cardiovascular diseases and other risk factors. In the elderly a large interindividual variability in drug disposition is particularly prominent. In conclusion, the complexity of interactions between comorbidity, polypharmacy, and age-related changes in pharmacokinetics (and pharmacodynamics) justify the old and well-known dosing aphorism " start low, go slow" for aged individuals.

journal_name

Curr Drug Metab

journal_title

Current drug metabolism

authors

Shi S,Klotz U

doi

10.2174/138920011796504527

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

601-10

issue

7

eissn

1389-2002

issn

1875-5453

pii

BSP/CDM/E-Pub/000171

journal_volume

12

pub_type

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