TY - JOUR T1 - Aging: changes in distribution of diazepam and metabolites in the rat. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 299 LP - 302 VL - 14 IS - 3 AU - A Rahman AU - H L Komiskey AU - W L Hayton AU - W P Weisenburger Y1 - 1986/05/01 UR - http://dmd.aspetjournals.org/content/14/3/299.abstract N2 - The brain levels of diazepam and its metabolites after a single iv injection of diazepam were measured over a 2-hr time period in young (3-4-month-old), mature (12-15-month-old), and senescent (29-31-month-old) male Fischer 344 rats. The areas under the brain level time curves were used as an index of exposure. Senescent rats were exposed to significantly more diazepam, N-desmethyldiazepam, and oxydiazepam between 0 and 120 min after an injection of 180 micrograms/kg of diazepam than the young or mature animals. The unbound plasma level failed to adequately account for the age-related increase in brain exposure to diazepam. Mechanisms other than the unbound diazepam in plasma are probably involved in eliciting the age-associated increase in brain levels of diazepam and its metabolites. ER -