Effect of fluticasone propionate nasal spray on bioavailability of intranasal hydromorphone hydrochloride in patients with allergic rhinitis.
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.


METHODS
Randomized, three-way, crossover pharmacokinetic study.


METHODS
University clinical research unit.


METHODS
Twelve patients with allergic rhinitis.


METHODS
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.


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 (Cmax) values were 3.02 and 3.56 ng/ml, respectively. No statistical differences in Cmax 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 Cmax (Tmax) values were significantly different (p=0.02) for treatments B and C (15 and 30 min, respectively) using rank-transformed Tmax for ANOVA. Adverse effects were consistent with known effects of hydromorphone administered by other routes, with the exception of bad taste after intranasal administration.


CONCLUSIONS
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.
Davis
George A
GA
Division of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington 40536-0293, USA. gadavi00@email.uky.edu
Rudy
Anita C
AC
Archer
Sanford M
SM
Wermeling
Daniel P
DP
McNamara
Patrick J
PJ
D000281:Administration, Intranasal; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004358:Drug Therapy / Q000379:methods; D005260:Female; D000068298:Fluticasone; D006801:Humans; D004091:Hydromorphone / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy*; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy*
D000730:Androstadienes; D000068298:Fluticasone; D004091:Hydromorphone