Aging: changes in distribution of diazepam and metabolites in the rat.
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.
Rahman
A
A
Komiskey
H L
HL
Hayton
W L
WL
Weisenburger
W P
WP
D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003975:Diazepam / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D003708:Nordazepam / Q000378:metabolism; D010076:Oxazepam / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344 / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D013693:Temazepam / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D003708:Nordazepam; D010076:Oxazepam; D013693:Temazepam; D003975:Diazepam