OXAZEPAM KINETICS - EFFECTS OF AGE AND SEX

Abstract

Healthy male and female volunteers (38), 22-84 yr old, 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 46 h after the dose. Absorption of oxazepam was relatively slow with peak plasma levels reaching an average of 2-3 h after dosage. Absorption (1st-order) was observed in only 22 of the 38 subjects. Elimination half-life [t1/2] ranged from 4.9-19.4 h and was longer (P < 0.05) in females (mean: 9.7 h) than in males (7.8 h); t1/2 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 and 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. Sex is a more important determinant of oxazepam clearance than is age.