Diazepam tissue distribution

In horses, diazepam is distributed widely to the tissues and metabolized extensively the values quoted for elimination half-life range from 3 to 22 h (Muir et al 1982). High doses of benzodiazepines cause muscle weakness, facial and neck muscle fasciculations, ataxia and recumbency. In neonatal foals, the i.v. administration of benzodiazepines can cause respiratory depression or arrest, through accumulation (Norman et al 1997), so resuscitation equipment should be available and repeated doses should be administered with extreme care. 

The more lipid-soluble the BZD, the more readily it passes from the plasma through the lipophilic blood-brain barrier and, thus, the more rapid its onset of action. BZDs can be subdivided on the basis of lipophilicity-a factor that plays an important role in absorption. Midazolam, quazepam, and diazepam are among the more lipophilic of the BZDs. Because increasing lipophilicity also increases the rate of redistribution from blood and brain into adipose tissue, BZDs that are less lipophilic may have more persistent brain concentrations due to reduced peripheral distribution ( 97, 184). 

The pharmacokinetic properties of the benzodiazepines in part determine their clinical use. In general, the drugs are well absorbed, widely distributed, and extensively metabolized, with many active metabolites. The rate of distribution of benzodiazepines within the body is different from that of other antiseizure drugs. Diazepam and lorazepam in particular are rapidly and extensively distributed to the tissues, with volumes of distribution between 1 L/kg and 3 L/kg. The onset of action is very rapid. Total body clearances of the parent drug and its metabolites are low, corresponding to half-lives of 20-40 hours. 

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