Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus.

Benzodiazepines are potent and effective drugs for the management of acute seizures and status epilepticus. Lorazepam, diazepam, and clonazepam have been the most widely studied of the benzodiazepines in the treatment of status epilepticus. In 47 studies of these drugs involving 1,455 patients, lasting control of status epilepticus was achieved in 79% of the patients. None of these benzodiazepines is clearly superior to another for the effective control of status epilepticus. Differences in pharmacokinetic parameters, therefore, will influence the choice of drug. All three benzodiazepines are lipid-soluble and enter the brain within seconds to minutes after intravenous administration. Diazepam, however, is very lipid-soluble and highly protein-bound and thus has a very large volume of distribution of unbound drug. As a result, the effective duration of action of diazepam in status epilepticus is only 20 to 30 min, whereas that of lorazepam, which has a much smaller volume of distribution of unbound drug, is at least several hours after a single intravenous injection. This allows the orderly administration of an antiepileptic drug for long-term seizure control after status epilepticus has been controlled. For this reason, lorazepam is preferable for the initial management of status epilepticus. Continuous intravenous infusion of diazepam has been used successfully in the management of some patients with status epilepticus refractory to initial treatment.