This review focuses on one of the key factors accounting for differences in drug/metabolite exposure in paediatric and elderly subjects compared with that of the adult population, that is, differences in drug metabolism (both qualitative and quantitative) and in particular differences due to changes in the activity and/or concentration of drug metabolizing enzymes. Important differences have been found in the paediatric population compared with adults for both phase I (e.g. CYP3A7 versus CYP3A4 and CYP1A2, reductive and hydrolytic enzymes) and phase II (e.g. glucuronosyltransferases) enzymes. In the elderly, some phase I enzymes (e.g. esterases) appear to be impaired. From the information collected thus far, it would appear that phase II reactions, though sometimes decreased, are not extensively affected by old age.
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