Bioavailability and tolerability of intranasal diazepam in healthy adult volunteers.
Epilepsy Res
; 84(2-3): 120-6, 2009 Apr.
Article
en En
| MEDLINE
| ID: mdl-19231138
ABSTRACT
Intranasal therapy has been proposed as an alternative for the management of seizure emergencies. The bioavailability, dose proportionality and tolerability of a supersaturated intranasal formulation of diazepam (DZP) solubilized in a glycofurol-water cosolvent system was investigated. Eight healthy volunteers were randomized into a single-blind, three-way crossover study to compare 5 and 10mg intranasal DZP doses of the investigational formulation with a 5mg dose of a DZP solution (DZP injectable, 5mg/mL) administered intravenously. Treatments were separated by a two-week washout period. Plasma samples for DZP analysis were collected pre-dose and at regular intervals up to 48h post-dose and assayed by HPLC. Visual analog scales (VAS) were used to assess tolerability (1-tolerable; 10-extremely intolerable) and pain (1-no pain; 4-extreme pain) at predefined time points. Following the 5 and 10mg doses, the median t(max) were 20 and 30min and the mean C(max) were 134.3+/-62 and 247.6+/-61ng/mL. Estimated bioavailability was 75% for both doses. Pain scores of 2 and 2.3 were observed following the 5 and 10mg doses; tolerability scores were 4.4 and 4.7. Pain and tolerability scores returned to baseline within 10h. Our formulation provided reasonable bioavailability, but was not well tolerated.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diazepam
/
Anticonvulsivantes
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Epilepsy Res
Asunto de la revista:
CEREBRO
/
NEUROLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos