title: Effect of age and gender on disposition of temazepam.
abstract: Thirty-two male and female volunteers, 24-84 years of age, ingested single 30-mg doses of temazepam, a 3-hydroxy-1,4-benzodiazepine derivative used as a hypnotic agent. Kinetics of total and unbound temazepam were determined from multiple plasma temazepam concentrations measured during 48 hr after the dose. The temazepam elimination half-life ranged from 8 to 38 hr and was longer in women than in men (16.8 versus 12.3 hr, p less than 0.05). Likewise, clearance of total temazepam (assuming complete absorption) was higher in men than in women (1.35 versus 1.02 ml/min/kg, p less than 0.025). Neither half-life nor clearance was significantly related to age. The volume of distribution of total temazepam (mean 1.40 liters/kg) was unrelated to age or gender. Temazepam was extensively protein bound, with a mean free fraction of 2.6% (range 12.7-3.4%). The free fraction increased with age (r = 0.45, p = 0.01), partly due to the inverse relation of the free fraction to plasma albumin concentration (r = -0.34, p = 0.06) and the age-related decline in plasma albumin (r = -0.49, p less than 0.005). After correction for individual differences in binding, clearance of unbound temazepam in men was higher than in women (50.5 versus 39.7 ml/min/kg, 0.05 less than p less than 0.01), and it tended to decline with age in both sexes (r = -0.44 and -0.43, respectively, p = 0.1).
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012737:Sex Factors; D012907:Smoking; D013693:Temazepam / Q000097:blood / Q000378:metabolism*
chemical_list: D014151:Anti-Anxiety Agents; D013693:Temazepam