Pharmacokinetics of buccal and intranasal lorazepam in healthy adult volunteers

Abstract

Intranasal lorazepam has more favourable pharmacokinetics than buccal lorazepam when considering the need for the rapid blood concentrations required for seizure termination. Further clinical evaluation of this route is required.

Buccal and intranasal lorazepam clinical pharmacokinetics: can it adequately compete with intravenous lorazepam in pediatric care patients?

“…With the exception of a significant time lag in absorption of lorazepam after buccal dosing (the first 30 min), the plasma profiles of lorazepam appeared to be similar between buccal and intranasal dosing options in human volunteers [3]. A closer inspection of plasma concentration versus time profiles for lorazepam following buccal and intrasal administration suggested that the mean peak levels achieved were 14-16 ng/mL and that by 12 h post-dosing the levels had declined to approximately 4 ng/mL [3]. Therefore, it is apparent that desired levels after either buccal or intranasal dosing should have been at least fourfold higher to achieve target levels for a meaningful clinical outcome.…”

“…This window of therapeutic levels of lorazepam is proposed based on the reports of excessive sedation if levels exceed 100 ng/mL and the lack of effective seizure control if level falls below a threshold of 40 ng/mL [10]. With the exception of a significant time lag in absorption of lorazepam after buccal dosing (the first 30 min), the plasma profiles of lorazepam appeared to be similar between buccal and intranasal dosing options in human volunteers [3]. A closer inspection of plasma concentration versus time profiles for lorazepam following buccal and intrasal administration suggested that the mean peak levels achieved were 14-16 ng/mL and that by 12 h post-dosing the levels had declined to approximately 4 ng/mL [3].…”

“…The intent of this communication is to provide additional thoughts and perspectives on the clinical pharmacokinetics of lorazepam, as well as to compare the pharmacokinetic data reported in the study of Anderson et al [3] with the population pharmacokinetic data established for clinical efficacy and/or pharmacodynamic activity of lorazepam in pediatric patients with and without epileptic seizures [10]. This endeavor is expected to provide clues for the rational development of alternate route(s) of administration, such as intranasal and/or buccal, should there be a promise for further optimization of the delivery options to achieve the desired pharmacodynamic and/or clinical outcomes.…”

“…This clinical pharmacokinetic study assumes high importance for the reason that intravenous lorazepam is now a drug of choice for the management of seizures in pediatric patients as compared to either diazepam or midazolam since it provides the benefit of prolonged efficacy with a lesser potential for side effects [1,4]. Given the anecdotal pharmacokinetic data reported in the literature for various routes [5][6][7][8][9], it was therefore important that the pharmacokinetics of lorazepam following buccal and intransal routes of dosing of lorazepam be re-examined, as achieved by Anderson et al in their single crossover study [3].…”

“…The recent report of Anderson et al probes the pharmacokinetic disposition of lorazepam when administered intranasally versus buccally in healthy human subjects [3]. This clinical pharmacokinetic study assumes high importance for the reason that intravenous lorazepam is now a drug of choice for the management of seizures in pediatric patients as compared to either diazepam or midazolam since it provides the benefit of prolonged efficacy with a lesser potential for side effects [1,4].…”