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- Title
Efficacy and tolerability of rupatadine at four times the recommended dose against histamine- and platelet-activating factor-induced flare responses and ex vivo platelet aggregation in healthy males M.K. Church Rupatadine at higher doses on inhibition of dermal flare
- Authors
Church, M. K.
- Abstract
European guidelines recommend increasing H-antihistamine doses up to fourfold in poorly responding patients with urticaria. To assess the efficacy and tolerability of high-dose rupatadine (40 mg) against platelet-activating factor (PAF)- and histamine-induced flare responses in human skin and to verify its anti-PAF activity by assessing its inhibition of PAF-induced platelet aggregation in the blood of subjects receiving rupatadine 40 mg. In the flare study, six male volunteers received a single dose of rupatadine 40 mg. Flares were induced before dosing and up to 96 h afterwards by intradermal PAF and histamine. In the e x vivo study, four male volunteers received an oral dose of rupatadine 40 mg and blood samples were taken 4 h afterwards. Platelet aggregation was assessed in platelet-rich plasma by incubation for 5 min with PAF. Rupatadine 40 mg reached maximal plasma levels of 15·1 ± 4·4 ng mL at 1 h and its metabolite, desloratadine, 5·2 ± 0·9 ng mL at 2 h. Neither was detectable at 12 h. Inhibition of histamine- and PAF-induced flares was significant within 2 h, maximal at 6 h (87·8 ± 3·1% and 87·1 ± 2·5% inhibition, respectively, P < 0·0001) and still statistically significant at 72 h. Rupatadine 40 mg inhibited PAF-induced platelet aggregation ex vivo by 82 ± 9% ( P = 0·023). A single oral dose of rupatadine 40 mg was well tolerated with mild transient somnolence being reported. A single dose of rupatadine at four times the recommended dose is well tolerated, highly effective for up to 72 h against PAF- and histamine-induced dermal flares and has demonstrable PAF-receptor antagonism ex vivo.
- Subjects
PLATELET activating factor; BLOOD platelet aggregation; TREATMENT of urticaria; HISTAMINE; BLOOD plasma
- Publication
British Journal of Dermatology, 2010, Vol 163, Issue 6, p1330
- ISSN
0007-0963
- Publication type
Article
- DOI
10.1111/j.1365-2133.2010.10029.x