Pharmacokinetics and pharmacodynamics of moist inhalation epinephrine using a mobile inhaler.
Eur J Clin Pharmacol
; 69(6): 1303-10, 2013 Jun.
Article
en En
| MEDLINE
| ID: mdl-23292159
ABSTRACT
BACKGROUND:
Intramuscular (L-)epinephrine is used as self-medication for serious hypersensitivity reactions. Inhalative administration has the theoretical advantage of a more rapid absorption and better controllability.OBJECTIVES:
The current trial was conducted to explore pharmacokinetics and pharmacodynamics of two nebulized inhalative epinephrine doses (4 mg and 8 mg in aqueous solution) using a mobile pocket inhaler relative to intramuscular administration (0.3 mg) and placebo.METHODS:
This randomized, open-label, change-over pilot study involved eight young healthy men and women. Noncompartmental pharmacokinetic and pharmacodynamic parameters were calculated from epinephrine plasma concentrations and hemodynamic parameters.RESULTS:
Mean exposure to epinephrine decreased from the 8 mg dose to the 4 mg inhalative dose, and further with the 0.3 mg intramuscular dose, with active treatments showing significantly higher concentrations than placebo (geometric mean area under the curve AUC0-t(last) values 282, 236, 204 and 81.6 hr*ng/L). Maximal concentrations were reached within approximately 15 min for all active treatments. Epinephrine effects for inhalative administrations on heart rates were significantly higher than those for the intramuscular or placebo administration, while no excessive effects occurred. Pronounced overall variability prohibited a definite assessment of relative bioavailability between treatments. However, results indicated that epinephrine concentrations obtained following the 8 mg inhalative dose were not inferior to those after 0.3 mg i.m.CONCLUSIONS:
A relevant fraction of moist inhalation epinephrine doses is absorbed and mediates systemic effects. This suggests that administration of epinephrine via a suitable pocket inhaler device may be beneficial in ambulatory emergency treatment of systemic hypersensitivity reactions. EudraCT number 2010-021493-11.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nebulizadores y Vaporizadores
/
Epinefrina
/
Agonistas Adrenérgicos
/
Antialérgicos
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania