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 Metabjournal_title
Current drug metabolismauthors
Shi S,Klotz Udoi
10.2174/138920011796504527subject
Has Abstractpub_date
2011-09-01 00:00:00pages
601-10issue
7eissn
1389-2002issn
1875-5453pii
BSP/CDM/E-Pub/000171journal_volume
12pub_type
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