Desmethyldiazepam kinetics in the elderly after oral prazepam

Abstract

Our subjects were 15 young (aged 22 to 42 yr) and 14 elderly (aged 62 to 85 yr) people who took single oral doses of 20 mg prazepam. Plasma desmethyldiazepam (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 to 20 hr. First-order DMDZ appearance was observed in only 17 subjects. Volume of distribution of total DMDZ (range, 1.33 to 6.30 l/kg) and of unbound DMDZ after correction for protein binding (range, 43 to 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 to 224 hr) rose with age in men (r = 0.66, p < 0.01) but not in women (r = -0.02). Clearance of unbound DMDZ (range, 2.9 to 31.2 ml/min/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.