Desmethyldiazepam kinetics in the elderly after oral prazepam

Abstract

The subjects were 15 young (22-42 yr old) and 14 elderly (62-85 yr old) people who took single oral doses of 20 mg prazepam, an antianxiety agent. Plasma demethyldiazepam (DMDZ) concentrations were determined in venous blood samples drawn up to 9 days after the dose. Appearance in blood of DMDZ was slow, with peak plasma levels reached in an average of 10-20 h. First-order DMDZ appearance was observed in only 17 subjects. Volume of distribution of total DMDZ (range 1.33-6.30 l/kg) and of unbound DMDZ after correction for protein binding (range, 43-243 l/kg) was larger in women than in men of all ages, and in the elderly as opposed to the young. Elimination half-life (range, 29-224 h) rose with age in men (r [correlation coefficient] = 0.66, P < 0.01) but not in women (r = -0.02). Clearance of unbound DMDZ (range, 2.9-31.2 ml/min per kg) was greater in women than in men of all ages, and declined with age in men (r = -0.40) but not in women (r = -0.06). As in the case of diazepam, age can influence DMDZ kinetics, but changes in drug disposition with age may differ between sexes.