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50 The influence of cetirizine on symptom generation and nasal eosinophilia in seasonal allergic rhinitis
VOLUME NUMBER
87 1, PART 2
Abstracts
49 PERSISTENT EFFICACY OF A COMBINATION ANTIHISTAMINE/ANALGESIC/DECONGESTANT PRODUCT (CAAD) THE MORNING AFTER A BEDTIME D. Pug&I&D.. A. m DOSE. W.M.D.. T.J. Wit& Dr.P.H.. Baltimore, MD ; Shelton, CI This study evaluated the effect of a single bedtime dose of CAAD (50 mg diphenhydramine, 60 mg pseudoephedrine and 1 g acetaminophen in 10% ethanol) on nasal challenge with antigen the next morning. A double blind three treatment, placebo (P) controlled cross-over study was done in 18 volunteers with a history of allergic rhinitis. Diphenhydramine HCI (D)(50 mg in 10% ethanol) taken 2 hours hefore scoring was used as a positive control. The treatment scheduleswere CAAD and P, P and P, or P and D (taken at bedtime lo-12 p.m. and next morning at 6 a.m., respectively). The volunteers reported to the lab at 8 a.m. for nasal provocation with increasing doses of antigen. Nasal lavages with saline were done 10 minutes after each challenge to monitor histamine and TAME-esterases activity. Sneezeswere counted. Do~~$~ Hrstamine(ng/ml) TAMl&p&osl &g5gs P 8.1f1.9 165.3f40.6 17.3f3.1 CAAD lO.lf2.8
137.6i31.2
51
In an incremental allergen challenge design more patients tolerated the highest challenge dose with SD (11/14) than with other treatments. SD was significantly better than PL on all efficacy measurements: nasal resistance (p&0.03), rhinorrhoea (pu).Ol), sneezing (pcO.01) and nasal itch (p&0.02). The T component of SD attributed primarily to the reduction in itch, sneeze and rhinorrhoea (+O.Ol) while the reduction in nasal airways resistance was primarily attributable to PS (pco.04). Adverse effects were carefully monitored on the different regimes, SD (47%), PS (36%). T (25%), P (20%), with insomnia and dry mouth predominating.
&ank&~~~total if1z2aEve d&en; 2) a= D significant yg CAAD, b= CAAD a P, c= D ys P This study shows that CAAD taken the night before, as expected, does not inhibit release of histamine from mast cells, but reduces allergic symptoms without causing drowsiness. We speculate that the effect observed was due to the diphenhydramine, but an interaction with the other components cannot be ruled out. The persistent efficacy 10 hours after administration may provide a rationale for using sedating antihistamines at bedtime to control allergic symptoms the next morning.
Forty one grass pollen sensitive seasonal rhinitic subjects participated in a doubleblind, placebo-controlled, randomized study of the protective effects of cetirizine 10 mg o.m. in seasonal allergic rhinitis. Each completed daily a diary card of their individual symptoms of nasal itch, sneeze, runny nose and nasal blockage and recorded their use of rescue medication (terfenadine 60 mg p.r.n.). All started as a cohort in May and took treatment for six weeks. Nasal smears for eosinophils were obtained pre-season, in-season and postseason while nasal biopsies, stained immunohistochemically with the monoclonal antibody EG2, were obtained in-season in 14 subjects on cetirizine (C) and 10 on placebo (P). Clinically C was significantly better than P in limiting itchy nose (p
of C
THE EFFECT OF SELDANE-D, TEBFENADINE AND PSEUDOEPHEDRINEON THE NASAL RESPONSETO ALLERGEN I. Feather, K. Harrison, H. Brewster, P.H. Howarth, Southampton, United Kingdom. Fourteen grass pollen sensitive seasonal rhinitic patients (lOM, 7F, age 19-56 yrs) participated in a double blind, placebocontrolled, four period, cross-over study to investigate the effect of pseudoephedrine (PS) 120 mg, terfenadine (T) 60 mg, Seldane-D (SD: combined PS 120 mg and T 60 mg) or matched placebo (PL) on the nasal response to allergen.
10.4f2.Ob 0:56i0:25 6 3fl 3 as 2.1M.48.C
50 THE INFLUENCE OF CETIRIZINE ON SYMPTOM GENERATION AND NASAL EOSINOPHILIA IN SEASONAL ALLERGIC RHINITIS. P.H. Howarth, S.J. Wilson, H. Brewster, Southampton, United Kingdom.
151
These findings identify the complementary protective effects of PS and T on the nasal response to allergen and suggest a potential SD in the treatment of allergic rhinitis.
52
for
COMPARISON OF TROUGH EFFECTS OF FIVE NONSEDATING ANTIHISTAMINES ON HISTAMINE-INDUCED WHEALAND FLARE REAcTK)Ns. P. Van Roov. M. Janssens, Janssen Research Foundation, Beerse, Belgium In a double-blind parallel group study with 5 groups of 6 volunteers, histamine-induced wheal and flare (W&F) reactions were evaluated before and after 1 week once daily treatment with either astemizole (A 10 mg), ebastine (E 10 mg), cetiririne (C 10 mg), ‘loratadine (L 10 mg) or terfenadine-forte (T 120 mg). At the end of treatment, skin tests were evaluated till 24 hours after the last dose (trough). Inhibition of W&F at trough was better with A and E than with C and L and especially than with T. which showed the poorest trough effects (% inhibition) : .wheal flare
45 70
39 67
55 72
42 64
Even after 1 week of treatment distinct differences were seen between peak and trough effects, mainly for T, but also for L and C and to a much lesser extent for A and E. The ratios between the percentage inhibition at trough vs at peak were the following for the 5 drugs (for a constant 24-hour inhibition this ratio should be 1): wheal flare
0.66 0.93
0.51 0.78
0.73 0.85
0.66 0.76
0.37 0.65
These results indicate that astemizole and ebastine are real once-daily drugs, whereas loratadine, cetirizine and especially the “once-daily” terfenadine show marked variatbns in antihistamine effects, so that they might not be fully effective for the entire 24-hour period.
87 1, PART 2
Abstracts
49 PERSISTENT EFFICACY OF A COMBINATION ANTIHISTAMINE/ANALGESIC/DECONGESTANT PRODUCT (CAAD) THE MORNING AFTER A BEDTIME D. Pug&I&D.. A. m DOSE. W.M.D.. T.J. Wit& Dr.P.H.. Baltimore, MD ; Shelton, CI This study evaluated the effect of a single bedtime dose of CAAD (50 mg diphenhydramine, 60 mg pseudoephedrine and 1 g acetaminophen in 10% ethanol) on nasal challenge with antigen the next morning. A double blind three treatment, placebo (P) controlled cross-over study was done in 18 volunteers with a history of allergic rhinitis. Diphenhydramine HCI (D)(50 mg in 10% ethanol) taken 2 hours hefore scoring was used as a positive control. The treatment scheduleswere CAAD and P, P and P, or P and D (taken at bedtime lo-12 p.m. and next morning at 6 a.m., respectively). The volunteers reported to the lab at 8 a.m. for nasal provocation with increasing doses of antigen. Nasal lavages with saline were done 10 minutes after each challenge to monitor histamine and TAME-esterases activity. Sneezeswere counted. Do~~$~ Hrstamine(ng/ml) TAMl&p&osl &g5gs P 8.1f1.9 165.3f40.6 17.3f3.1 CAAD lO.lf2.8
137.6i31.2
51
In an incremental allergen challenge design more patients tolerated the highest challenge dose with SD (11/14) than with other treatments. SD was significantly better than PL on all efficacy measurements: nasal resistance (p&0.03), rhinorrhoea (pu).Ol), sneezing (pcO.01) and nasal itch (p&0.02). The T component of SD attributed primarily to the reduction in itch, sneeze and rhinorrhoea (+O.Ol) while the reduction in nasal airways resistance was primarily attributable to PS (pco.04). Adverse effects were carefully monitored on the different regimes, SD (47%), PS (36%). T (25%), P (20%), with insomnia and dry mouth predominating.
&ank&~~~total if1z2aEve d&en; 2) a= D significant yg CAAD, b= CAAD a P, c= D ys P This study shows that CAAD taken the night before, as expected, does not inhibit release of histamine from mast cells, but reduces allergic symptoms without causing drowsiness. We speculate that the effect observed was due to the diphenhydramine, but an interaction with the other components cannot be ruled out. The persistent efficacy 10 hours after administration may provide a rationale for using sedating antihistamines at bedtime to control allergic symptoms the next morning.
Forty one grass pollen sensitive seasonal rhinitic subjects participated in a doubleblind, placebo-controlled, randomized study of the protective effects of cetirizine 10 mg o.m. in seasonal allergic rhinitis. Each completed daily a diary card of their individual symptoms of nasal itch, sneeze, runny nose and nasal blockage and recorded their use of rescue medication (terfenadine 60 mg p.r.n.). All started as a cohort in May and took treatment for six weeks. Nasal smears for eosinophils were obtained pre-season, in-season and postseason while nasal biopsies, stained immunohistochemically with the monoclonal antibody EG2, were obtained in-season in 14 subjects on cetirizine (C) and 10 on placebo (P). Clinically C was significantly better than P in limiting itchy nose (p
of C
THE EFFECT OF SELDANE-D, TEBFENADINE AND PSEUDOEPHEDRINEON THE NASAL RESPONSETO ALLERGEN I. Feather, K. Harrison, H. Brewster, P.H. Howarth, Southampton, United Kingdom. Fourteen grass pollen sensitive seasonal rhinitic patients (lOM, 7F, age 19-56 yrs) participated in a double blind, placebocontrolled, four period, cross-over study to investigate the effect of pseudoephedrine (PS) 120 mg, terfenadine (T) 60 mg, Seldane-D (SD: combined PS 120 mg and T 60 mg) or matched placebo (PL) on the nasal response to allergen.
10.4f2.Ob 0:56i0:25 6 3fl 3 as 2.1M.48.C
50 THE INFLUENCE OF CETIRIZINE ON SYMPTOM GENERATION AND NASAL EOSINOPHILIA IN SEASONAL ALLERGIC RHINITIS. P.H. Howarth, S.J. Wilson, H. Brewster, Southampton, United Kingdom.
151
These findings identify the complementary protective effects of PS and T on the nasal response to allergen and suggest a potential SD in the treatment of allergic rhinitis.
52
for
COMPARISON OF TROUGH EFFECTS OF FIVE NONSEDATING ANTIHISTAMINES ON HISTAMINE-INDUCED WHEALAND FLARE REAcTK)Ns. P. Van Roov. M. Janssens, Janssen Research Foundation, Beerse, Belgium In a double-blind parallel group study with 5 groups of 6 volunteers, histamine-induced wheal and flare (W&F) reactions were evaluated before and after 1 week once daily treatment with either astemizole (A 10 mg), ebastine (E 10 mg), cetiririne (C 10 mg), ‘loratadine (L 10 mg) or terfenadine-forte (T 120 mg). At the end of treatment, skin tests were evaluated till 24 hours after the last dose (trough). Inhibition of W&F at trough was better with A and E than with C and L and especially than with T. which showed the poorest trough effects (% inhibition) : .wheal flare
45 70
39 67
55 72
42 64
Even after 1 week of treatment distinct differences were seen between peak and trough effects, mainly for T, but also for L and C and to a much lesser extent for A and E. The ratios between the percentage inhibition at trough vs at peak were the following for the 5 drugs (for a constant 24-hour inhibition this ratio should be 1): wheal flare
0.66 0.93
0.51 0.78
0.73 0.85
0.66 0.76
0.37 0.65
These results indicate that astemizole and ebastine are real once-daily drugs, whereas loratadine, cetirizine and especially the “once-daily” terfenadine show marked variatbns in antihistamine effects, so that they might not be fully effective for the entire 24-hour period.