Galenic Formulation of Midazolam (MDZ) Intranasal(IN): Evaluation of plasma levels and tolerance in healthy volunteers in Argentina

PACHA M.S.; KRIEBAUM M.; MARTINEZ O.; BRAMUGLIA G.F.; KRAVETZ M.C.; BUONTEMPO F.; OTAMENDI E.; CHIAPPETTA D.A.

Encuentro; American Academy of Neurology 67th Annual Meeting; 2015

American Academy of Neurology

Objectives: To determine MDZ plasma levels after IN administration of a Galenic formulation of MDZ in healthy volunteers and to describe the tolerance of MDZ IN. Background: The treatment of choice for acute seizures are Benzodiazepines (BDZ). MDZ IN could be a very useful therapeutic tool for acute attacks, but this formulation is not commercially available in Argentina. Therefore we developed a Galenic formulation of MDZ IN. Design / Methods: The trial was approved by the institutional review board (IRB) of our Hospital. 4 healthy volunteers (3 male, 1 female) gave their Informed Consent for the study. They received a single 4 mg dose MDZ IN. The nasal spray formulation consisted of 2.5[percnt] (w/ v) of MDZ, Propylene glycol, and water. Blood samples were drawn at 10 minutes, 1 and 2 hours after the application. Volunteers should report any side effects. Results: 10 minutes after administration, the MDZ plasma levels were: mean 11.6 ng / ml (SD: 4.6 ng / ml). 1 hour later, the mean was 8.9 ng / ml (SD: 7.7) ng / ml, and at 2 hours the mean was 2.1 ng / ml (SD: 2 ng / ml). The dose of 4 mg of MDZ IN was well tolerated. 2 volunteers reported mild local irritation. 3 volunteers had mild sedative effects. Conclusions: We could determine MDZ plasma levels after administration of the Galenic formulation of MDZ IN. Although the dose used was low, plasma levels were detected within minutes of administration. The adverse effects of this route of administration were mild and tolerable. This is the first report of a Galenic formulation of MDZ IN in Argentina.