ABSTRACT
Single oral doses (5, 10 and 15 mg) of the new H1-receptor antagonist 3,7-dihydro-7-[2-hydroxy-3-[4-[3-phenylthio) propyl]-1-piperazinyl]propyl-1,3-dimethyl-1H-purine-2,6-dione dihydrochloride (tazifylline, RS-49014) were administered at 7-day intervals to 12 atopic and 12 non-atopic volunteers in a double-blind randomised cross-over study. Antiallergic activity was evaluated from pre to 60 min post dose inhibitions of wheal and flare areas provoked by various cutaneous challenges. Atopic subjects showed greater skin reactivity than non-atopics to some challenges. Tazifylline was associated (in atopics and non-atopics) with statistically significant dose related inhibitions, of flare over 5-15 mg and of wheal (10-15 mg) induced by the more potent and reproducible challenges of codeine, 1% histamine and anti-IgE. Antiallergic activity of tazifylline in the 10-15 mg dose range was superior to 5 mg without the intervention of clinically significant sedative effects at any of the 3 dose levels tested.
Subject(s)
Histamine H1 Antagonists/therapeutic use , Hypersensitivity, Immediate/drug therapy , Theophylline/analogs & derivatives , Adult , Clinical Trials as Topic , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Random Allocation , Skin Tests , Theophylline/therapeutic useABSTRACT
In a group of 45 patients with mild to moderately severe claudication studied over the same 4-month period, cinnarizine administration (75 mg 3-times daily) was associated with a greater than 20% improvement in walking distance in 65% of the patients, who derived significantly more benefit than the 30% of placebo responders. The mean improvement in walking distance was 11% for the placebo group compared to 142% for cinnarizine-treated patients. An open 12-month follow-up showed that improvements in walking distance with cinnarizine were maintained in all 12 patients, whereas in the 10 control patients only 10% reported improvement. Objectively, significant plethysmographic improvements were detected only for the cinnarizine-treated patients and shown by an increase in arterial flow-pressure dynamics of the lower limbs.
