title: Diazepam disposition determinants.
abstract: Factors influencing diazepam kinetics were assessed in 4 equal groups (n = 11) of young male and female (aged 21 to 37 yr) and elderly male and female (aged 61 to 84 yr) subjects, all of whom were healthy. In all 44, plasma diazepam concentrations were determined by electron-capture gas-liquid chromatography in multiple samples drawn for as long as 9 days after a single 5- to 10-mg intravenous dose. Based upon total (bound + free) diazepam concentrations, volume of distribution (Vd) ranged from 0.7 to 4.7 l/kg, and became larger both with increasing age and with female sex. Clearances of total (bound + free) diazepam in young and elderly females were nearly identical (0.51 and 0.48 ml/min/kg), but clearance was higher in young than elderly males (0.39 and 0.24 ml/min/kg, p less than 0.01). The unbound fraction of diazepam in plasma (range, 0.9% to 2.7%) did not depend on sex, but was greater in the elderly than in the young. In part this related to lower plasma albumin concentrations in the elderly. After correction of kinetic data for individual differences in free fraction, Vd was larger in the females than in the males, but the effect of age was small. Clearance of unbound diazepam (intrinsic clearance) tended to be higher in the females than in the males of both age groups, and was higher in the young than in the elderly of both sexes (male: 29.9 and 14.9 ml/min/kg, p less than 0.005; female: 43.6 and 28.0 ml/min/kg, p less than 0.05). Smoking was associated with higher clearance values, particularly among young subjects.
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001835:Body Weight; D003975:Diazepam / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012737:Sex Factors; D012907:Smoking
chemical_list: D003975:Diazepam