PMID: 6106490Jan 1, 1980Paper

Effects of age and other drugs on benzodiazepine kinetics

Arzneimittel-Forschung
D J Greenblatt, R I Shader

Abstract

Because benzodiazepine derivatives are biotransformed by a variety of metabolic pathways, it is not surprising that age has varying effects on their kinetic properties. Both chlordiazepoxide and diazepam are biotransformed by hepatic N-demethylation. The aging process is associated with prolonged half-life and reduced clearance of both of these drugs. Sex may also influence their kinetics. In the case of diazepam, aging effects may be masked by alterations in protein binding. Desmethyldiazepam and desalkylflurazepam are biotransformed by hydroxylation. Old age tends to be associated with reduced clearance of these two compounds, particularly among elderly males, but age explains a relatively small portion of individual variation in their kinetics. Oxazepam, lorazepam, and temazepam undergo glucuronidation. Age has a relatively minor effect on the kinetics of these compounds. In general, altered hepatic clearance in the elderly does not necessarily predict changes in drug sensitivity, since many factors complicate the relation between blood concentrations and clinical response. Drug interactions with benzodiazepine derivatives are relatively uncommon and generally are not of clinical significance. Antacid coadministration reduce...Continue Reading

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