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Effect of Fluticasone Propionate Nasal Spray on Bioavailability of Intranasal Hydromorphone Hydrochloride in Patients with Allergic Rhinitis
Author(s) -
Davis George A.,
Rudy Anita C.,
Archer Sanford M.,
Wermeling Daniel P.,
McNamara Patrick J.
Publication year - 2004
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.24.1.26.34810
Subject(s) - fluticasone propionate , nasal administration , cmax , hydromorphone , bioavailability , nasal spray , pharmacokinetics , medicine , fluticasone , pharmacology , anesthesia , inhalation , opioid , receptor
Study Objective. To investigate the effect of the nasal corticosteroid fluticasone propionate on the bioavailability and pharmacokinetics of single‐dose intranasal hydromorphone hydrochloride in patients with allergic rhinitis. Design. Randomized, three‐way, crossover pharmacokinetic study. Setting. University clinical research unit. Patients. Twelve patients with allergic rhinitis. Intervention. Hydromorphone hydrochloride 2.0 mg was administered by intravenous infusion (treatment A), intranasal spray without allergic rhinitis treatment (treatment B), and intranasal spray after 6 days of fluticasone propionate (treatment C). Blood samples were collected serially from 0–16 hours. Measurements and Main Results. Pharmacokinetic parameters were determined by noncompartmental methods. An analysis of variance (ANOVA) model was used for statistical analysis. Mean (% coefficient of variation) absolute bioavailability of intranasal hydromorphone was 51.9% (28.2) and 46.9% (30.3) in patients with allergic rhinitis with and without treatment with fluticasone propionate, respectively. Mean maximum concentration (C max ) values were 3.02 and 3.56 ng/ml, respectively. No statistical differences in C max and area under the concentration versus time curve were detected between intranasal treatments. Bioavailability values for both intranasal treatments were lower than those in healthy volunteers (57%). Median time to C max (T max ) values were significantly different (p=0.02) for treatments B and C (15 and 30 min, respectively) using rank‐transformed T max for ANOVA. Adverse effects were consistent with known effects of hydromorphone administered by other routes, with the exception of bad taste after intranasal administration. Conclusion. Hydromorphone was rapidly absorbed after nasal administration, with maximum concentrations occurring for most subjects within 30 minutes. Allergic rhinitis may affect pain management strategies for intranasal hydromorphone, with a delay in onset of action for patients treated with fluticasone propionate.