Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

7. Project III: Transmucosal nasal delivery of low-dose midazolam – evaluation of two preparations for procedural anxiolysis
Due to his excellent experiences with i.v. anxiolysis during a former MRI examination, after
administration of the initial nasal dose of midazolam he requested i.v. application of an anxiolytic
treatment.
Generally, if anxiolysis of the initial treatment with 1 mg midazolam (MD or UD) was not sufficient to
perform MRI examination, one additional dose of 1 mg midazolam was administered.
All patients, refusing or interrupting the MRI examinations (therapy failures, n=3) were treated with
2 mg midazolam. Probably in these cases, diffuse anxiety and/or claustrophobia were too intense
to be cured with low-doses of midazolam (1-2 mg). But due to small number of patients requiring
2 mg midazolam, statistical analysis of the intensity of anxiety is not reasonable.
Acquired data of one patient had to be excluded from final analysis, because of protocol deviation.
This patient of the comparator group was initially treated with UD nasal spray but the additional
dose was administered by MD nasal spray.
As anxious patients are generally agitated they tend to move during MRI examination impairing
image quality by generating motion artifacts. In a prospective double-blind placebo controlled
randomized trial Hollenhorst et al. demonstrated significant reduction of MRI related anxiety in
patients receiving nasal midazolam, and the reported anxiety reduction correlated with improved
image quality. In the present multicenter study with nasal midazolam, overall 91 patients (MD n=42
and UD n=49) were treated 1 mg nasal midazolam (initial dose). All of them successfully completed
MRI examination and the generated MRI images were of good or even excellent quality.
No patient fell asleep and therefore all patients were able to appropriately respond to instructions
given during MRI examination. All MRI examinations were rated as normally feasible by radiologic
technician. Beside local irritation for both tested midazolam nasal spray no adverse drug reaction
was reported.
The parameters to assess the benefit of nasal anxiolysis for anxious patients undergoing MRI
examination were: anxiety score before medication and after completing of the MRI examination,
tolerance of nasal administration, local irritation, and willingness to repeat the MRI examination with
the analog medication receiving in the study.
Regarding subjective anxiety reduction, willingness to repeat the procedure, and diagnostic image
quality, the tested nasal sprays (MD and UD) were equivalent. Concerning convenience of
administration (i.e., delivery independent of position) and hygienic security UD nasal spray was
rated as superior to MD nasal spray.
Katja Suter-Zimmermann Page 94 of 188 University of Basel, 2008