Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

Table 2

Changes in the cytochrome P450 activity with ageing.

CYP Enzyme	Change with ageing	Probe drug used	Confounding factors
CYP1	↓	Theophylline	Ethnic polymorphisms, sex differences, lifestyle, and disease
CYP2CYP2C9CYP2C19	↓ (~25%)	PhenytoinWarfarinOmeprazole	Age-related effects, and unrecognised environmental effects, and pharmacogenetic variation
CYP2D6	↓ Older women↓ Older Japanese men	DextromethorphanHaloperidol	Genetic polymorphisms
CYP2E1	↓ Aged rats↔ Aged mice↓ Activity in human liver microsomes↔ Human hepatocytes	Chlorzoxazone	? Gender-conflicting results Polymorphisms
CYP3ACYP3A4	↓ Aged rodents↔ Humans↑ CL in women, no age effects	Cyclosporine, Erythromycin, Verapamil, Midazolam	InducersInducers
Multiple	↓	Antipyrine	Metabolised by CYP3A4, 1A2 and 2C8/9

CYP, cytochrome P450; ↓, decreased; ↑, increased; ↔, no change; ?, unknown; CL, clearance; adapted from [13, 52–55].