Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis.
BACKGROUND
Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide.


OBJECTIVE
To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide).


METHODS
During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 microg and an aqueous solution of budesonide 128 microg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8-10 days, were used in the analysis.


RESULTS
Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P<0.01-0.001). There was no overall difference in efficacy between rofleponide palmitate 400 microg and budesonide 128 microg.


CONCLUSIONS
Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 microg of rofleponide palmitate is similar to that of 128 microg of budesonide in the pollen-season model used in this study.
Ahlström-Emanuelsson
C
C
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
Andersson
M
M
Persson
C
C
Schrewelius
C
C
Greiff
L
L
D000281:Administration, Intranasal; D000305:Adrenal Cortex Hormones; D000328:Adult; D000485:Allergens; D000704:Analysis of Variance; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010168:Palmitates / Q000008:administration & dosage* / Q000627:therapeutic use; D011058:Pollen; D011355:Prodrugs / Q000008:administration & dosage* / Q000627:therapeutic use; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000276:immunology; D012621:Seasons
D000305:Adrenal Cortex Hormones; D000485:Allergens; D005938:Glucocorticoids; D010168:Palmitates; D011355:Prodrugs; C488032:rofleponide palmitate; D019819:Budesonide