June 16, 2003: What is the bioavailability of rectally administered benzodiazepines?

Diazepam and lorazepam are the two drugs most frequently administered rectally to control seizures.  Both are highly lipid soluble and therefore are absorbed well through rectal tissue.  There have been few studies of rectal administration of lorazepam.  In adult males, rectal absorption is variable, with 50-100% bioavailability (amount actually reaching the bloodstream) following rectal administration.  Peak concentrations of diazepam can be reached in 4-20 minutes following rectal administration (0.7 mg/kg) Rectal absorption of diazepam is also variable. (50+/-17 % bioavailability)

Regarding rectal administration, solutions are more rapidly absorbed than suppositories.  Suppository forms (the usual method of administration) are slowly and erratically absorbed with highly variable bioavailabilities.  This is true for both acetaminophen and benzodiazepine suppositories. 

The last question discussed the bioavailability of rectal APAP.  The evidence is that one needs to administer approximately 40 mg/kg rectally to obtain therapeutic APAP concentrations.  The evidence is more nebulous for benzodizapeines. Be aware that you usually will not get the same serum concentration with rectal administration that you will when you administer the drugs intravenously.

Thanks to Marty Baker Pharm D. for research on question of the week.

Graves NM, Kriel RL. Rectal administration of antiepileptic drugs in children.  Pediatr Neurol 1987;3:321-26

Rey E, Treluyer J. Pons G.  Pharmacokinetic optimization of benzodiazepine therapy for acute seizures: focus on delivery routes.  Clin Pharmacokinet 1999;36 (6) 409-24

Question of the week will be sent every two weeks during the summer.  Hope to see you at Tennessee ACEP.  I will be giving a lecture on the 23rd. 

I am interested in any questions that you would like answered.  Please e-mail me with any suggestions at donna.seger@vanderbilt.edu

Donna Seger, M.D.
Medical Director
Middle Tennessee Poison Center