6.3 Biological half-life by route of exposure
The terminal elimination half-life of diazepam ranges from approximately 24 hours to more than two days. With chronic dosing, steady state concentrations of diazepam are achieved between 5 days to 2 weeks. The half-life is prolonged in the elderly and in patients with cirrhosis or hepatitis. It is shortened in patients taking drugs which induce hepatic enzymes, included anticonvulsants. The active metabolite desmethyldiazepam has a longer half-life than
diazepam, and takes longer to reach steady state concentrations. (Klotz et al, 1976a; Mandelli et al, 1978;
Klotz et al.,1975; Andreasen et al., 1976).
A sample of 48 healthy male volunteers ranging in age from 18 to 44 years demonstrated variable pharmacokinetic parameters. This demonstrates the need for further understanding of the variables which determine diazepam absorption, distribution, metabolism, and elimination (Greenblatt et al., 1989).