The rates of oral absorption depend on the lipophilicity of the drugs. Most sedative-hypnotics are highly lipid soluble and exert their actions fast.

Redistribution is when highly lipid soluble drugs distribute to the brain, heart and kidneys very fast and then redistributes to the muscle and fat tissue.

Hepatic metabolism accounts for the clearance of all benzodiazepines.Most benzodiazepines undergo microsomal oxidation (phase 1 reaction), including dealkylationand hydroxylation catalyzed by cytochrome P450 enzymes.The metabolites are subsequently conjugated (phase 2 reaction) to form glucuronides that are excreted in the urine. Manyphase 1 metabolites of benzodiazepines are pharmacologically active.

The metabolism of several commonly used benzodiazepines including diazepam, midazolam and triazolam is affected by inhibitors and inducers of cytochrome P450 isozymes, because these benzodiazepines are mainly metabolized by these enzymes and inhibition of these isozyme may cause prolonged action of theses drugs.

BD not dependent on cytochrome P450 enzyme metabolism:

• oxaxepam
• lorazepam
• temazepam
• lormetazepam

the drugs are preferred in patients with compromised cytochrome P450 activity.