(Both liver mass and blood flow
decrease about 40%)
(3) Decreased first pass
(4) Phase I metabolic reactions decline.
(a) Hydroxylation (phenytoin)
(b) Dealkylation (benzodiazepines)
(c) Sulfide oxidation (chlorpromazine)
(d) Hydrolysis (aspirin)
(e) Nitro reduction (chloramphenicol)
These changes influence the pharmacokinetics of numerous agents
used by the elderly. Drugs with a high intrinsic clearance (eg
propranolol) have hepatic blood flow as a rate-limiting step.
Such drugs would have an increased bioavailability when both
hepatic blood flow and extraction are diminished. Therefore,
drugs with a high bioavailability such as antiarrhythmics should
be administered at the lowest recommended doses and monitored
Other factors such as
polypharmacy, alcohol use, smoking etc may influence metabolism
more significantly than age alone.
[Agents known to have decreased hepatic clearance in the
elderly]: acetaminophen, antiarrhymics, anticonvulsants,
antidepressants, antipsychotics, benzodiazepines, indomethacin,
theophylline, warfarin, some beta blockers.