Morphine pharmacokinetics after pulmonary administration from a novel aerosol delivery system.
Clin Pharmacol Ther
; 62(6): 596-609, 1997 Dec.
Article
en En
| MEDLINE
| ID: mdl-9433388
ABSTRACT
BACKGROUND:
Successful pharmacotherapy of pain often depends on the mode of drug delivery. A novel, unit dose, aqueous aerosol delivery system (AERx Pulmonary Drug Delivery System) was used to examine the feasibility of the pulmonary route for the noninvasive systemic administration of morphine.METHODS:
The study had two parts (1) a dose-ranging study in four subjects with three consecutive aerosolized doses of 2.2, 4.4, and 8.8 mg (nominal) morphine sulfate pentahydrate at 40-minute intervals, and (2) a crossover study, on separate days, in six subjects with 4.4 mg (nominal) aerosolized morphine sulfate administered over 2.1 minutes on three occasions and intravenous infusions of 2 and 4 mg over 3 minutes. Subjects were healthy volunteers from 19 to 34 years old. Arterial blood was sampled for a total of 6 hours and plasma morphine concentrations were measured by gas chromatography-mass spectrometry.RESULTS:
In part 1, plasma morphine concentrations were proportional to dose. In part 2, the mean +/- SD peak plasma concentration (Cmax) occurred at 2.7 +/- 0.8 minutes after the aerosol dose, with mean values for Cmax of 109 +/- 85, 165 +/- 22, and 273 +/- 114 ng/ml for the aerosol and 2 and 4 mg intravenous doses, respectively. The bioavailability [AUC(0-360 min)] of aerosol-delivered morphine was approximately 100% relative to intravenous infusion, with similar intersubject variability in AUC for both routes (coefficient of variation < 30%).CONCLUSION:
The time courses of plasma morphine concentrations after pulmonary delivery by the AERx system and by intravenous infusions were similar. This shows the utility of the pulmonary route in providing a noninvasive method for the rapid and reproducible systemic administration of morphine if an appropriate aerosol drug delivery system is used.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Analgésicos Opioides
/
Morfina
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Año:
1997
Tipo del documento:
Article
País de afiliación:
Australia