Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers

Epilepsia
Lindy L BanckeBarry E Gidal

Abstract

To compare the pharmacokinetics, pharmacodynamics, and tolerability of USL261, a midazolam formulation optimized for intranasal delivery, versus midazolam intravenous (IV) solution administered intranasally (MDZ-inj IN) or intravenously (MDZ-inj IV) in healthy adults. In this phase 1, five-way crossover, open-label study, 25 healthy adults (aged 18-42 years) were randomly assigned to receive 2.5, 5.0, and 7.5 mg USL261; 2.5 mg MDZ-inj IV; and 5.0 mg MDZ-inj IN. Blood samples were collected for 12 h post dose to determine pharmacokinetic profiles. Pharmacodynamic assessments of sedation and psychomotor impairment also were conducted. Adverse events, oxygen saturation, and vital signs were recorded. Increasing USL261 dose corresponded with increases in midazolam area under the concentration time curve (AUC) and maximum observed plasma concentration (Cmax ), with all doses demonstrating rapid median time to Cmax (Tmax ; 10-12 min). USL261 also demonstrated increased absorption, with a 134% relative bioavailability, compared with the same MDZ-inj IN dose. USL261 was associated with dose-dependent increases in sedation and psychomotor impairment (p < 0.05); however, these effects lasted <4 h and generally did not differ from MDZ-inj...Continue Reading

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Citations

Mar 1, 2016·Current Treatment Options in Neurology·Juan G Ochoa, William A Kilgo
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Aug 31, 2018·Epilepsia·Patricia D MaglalangJames C Cloyd
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Aug 20, 2021·Journal of Drug Assessment·Boulenouar MesraouaAli A Asadi-Pooya

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