Lorazepam
Clinical Need
Ten percent of the U.S. population is expected to have seizures sometime in their lifetime, many requiring emergency interventions, according to epidemiological statistics. Prolonged or repetitive seizures can be life-threatening and cause neurological damage, which makes the effectiveness of initial interventions particularly important. Intravenously administered lorazepam or diazepam currently is standard care, but many circumstances and conditions make it difficult for paramedics to administer IV drugs. Rectal diazepam gel is the only drug approved for treating acute repetitive seizures in children outside a hospital setting.
Product Benefit
ITI’s patented lorazepam nasal spray is initially being developed for the treatment of epileptic seizures. We believe that our product ultimately lends itself to all types of seizures in a variety of settings because of its anticonvulsant properties and emergency-ready attributes, i.e. rapid onset of action and ease of administration. As a result, intranasal lorazepam may potentially assist patients who experience prolonged or repetitive seizures, including alcohol-related, febrile and epileptic seizures. It could be used by caregivers at home, emergency management staff prior to transporting patients to the hospital, and medical professionals in the emergency room. As a benzodiazepine, intranasal lorazepam also is a good candidate for sedation and anxiety relief in surgical procedure settings.
Development Status
We have submitted an IND to meet requirements for a 505(b)(2) NDA. In addition, we have conducted one clinical trial in healthy volunteers comparing intranasal, intramuscular (IM) and intravenous (IV) administration of lorazepam. We found that intranasal lorazepam had 78% bioavailability compared to the IV dose; was absorbed rapidly and achieved clinically meaningful concentrations; and reached time-to-maximum concentration many times faster than IM delivery. Furthermore, no significant adverse effects were noted. Additional information on this study can be found in our publication (Wermeling et al., 2001). Follow-up studies are being developed.
U.S. Patent No. 6,610,271 for lorazepam nasal spray was issued on August 26, 2003 to the University of Kentucky with which we contracted to research and develop the lorazepam nasal spray. The patent entails a complete product concept, including the route of administration, delivery device and formulation. The patent’s inventor, Daniel Wermeling, Pharm.D., is ITI’s Chief Scientific Officer.
ITI Publication
Wermeling DPH, Miller JL, Archer SM, Manaligod JM, Rudy AC. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol 2001;41:1225-1231.
