Rahman A, Komiskey H L, Hayton W L, Weisenburger W P
Drug Metab Dispos. 1986 May-Jun;14(3):299-302.
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.
在2小时的时间段内，测定了年轻（3 - 4月龄）、成熟（12 - 15月龄）和衰老（29 - 31月龄）雄性Fischer 344大鼠单次静脉注射地西泮后其大脑中地西泮及其代谢产物的水平。大脑水平时间曲线下的面积被用作暴露指标。在注射180微克/千克地西泮后，衰老大鼠在0至120分钟内接触到的地西泮、N - 去甲基地西泮和奥沙西泮显著多于年轻或成熟动物。游离血浆水平未能充分解释大脑对地西泮暴露的年龄相关增加。血浆中游离地西泮以外的机制可能参与引发地西泮及其代谢产物大脑水平的年龄相关增加。
