Oxazepam kinetics: effects of age and sex

Thirty-eight healthy male and female volunteers, 22 to 84 years of age, ingested single 30-mg doses of oxazepam tablets in the fasting state. Oxazepam plasma concentrations were determined by electron-capture gas-liquid chromatography in multiple samples drawn during 48 hr after the dose. Absorption of oxazepam was relatively slow with peak plasma levels reached an average of 2 to 3 hr after dosage. First-order absorption was observed in only 22 of the 38 subjects. Elimination half-life ranged from 4.9 to 19.4 hr and was longer (P < .05) in females (mean: 9.7 hr) than in males (7.8 hr). Half-life was not associated with age in males but tended to increase with age in females (r = 0.45). Oxazepam was extensively bound to plasma protein. The mean free fraction was 4.3% and did not differ between sexes. Free fraction tended to increase with age (r = 0.25), in part because of significantly lower plasma albumin concentrations in the elderly (r = -0.58). Assuming 100% systemic availability, clearance of total as well as unbound oxazepam was significantly greater in men than in women. Intrinsic clearance tended to decline with age in men (r = -0.21) and women (r = -0.24) but these associations were not significant. Higher oxazepam clearance was associated with heavy cigarette smoking but this did not explain the sex-related difference. Thus, sex is a more important determinant of oxazepam clearance than is age.