Efficacy of mizolastine, a new antihistamine, compared with placebo in the treatment of chronic idiopathic urticaria.

A two-centre, double-blind, randomized, placebo (P)-controlled, parallel-group study was conducted in the UK to examine the efficacy and safety of mizolastine (M), a new H1-receptor antagonist, as a once-daily 10-mg dose in chronic idiopathic urticaria. Fifty-six outpatients (M: n = 28; P: n = 28) with a mean age of 38 +/- 15 years, a duration of disease of more than 3 years, and symptoms of urticaria at least twice a week in the absence of treatment were recruited. After a single-blind placebo run-in period, patients were allocated to one of two treatment groups and were evaluated after 7 and 28 days. The main characteristics (age, duration of disease, number of urticarial episodes, and total score) of the two groups were comparable at inclusion. Mizolastine was shown to improve the urticaria symptoms: at the end of the study, mizolastine produced a significantly greater decrease in the global symptom score comprising itch, wheals, and erythema (M: 2.1 +/- 2.1 vs P: 0.4 +/- 2.0; P = 0.002). The patient-rated global discomfort from symptoms measured by visual analog scale was significantly improved with mizolastine (M: 31.4 +/- 36.7) compared to placebo (P: 5.4 +/- 27.6; P = 0.003), with respectively more M responders (74.1%) than P responders (28.6%, P = 0.001), a responder being a patient with a > or = 50% decrease in VAS. Premature dropouts due to lack of efficacy and loss to follow-up mainly occurred at the first evaluation (day 7) and were more often observed in patients in the placebo group (n = 17) than in the mizolastine group (n = 8) (P = 0.031). No serious adverse events were recorded. Somnolence was reported in two mizolastine patients, one of whom discontinued the study. Thus, mizolastine may be considered a new treatment option for the symptoms of chronic urticaria.

The psychomotor and cognitive effects of litoxetine in young and middle aged volunteers.

1. The effects of a range of doses of litoxetine (twice daily for 4 days), a novel specific serotonin re-uptake inhibitor, were evaluated in young and middle aged volunteers. 2. Psychometric testing was carried out at various time points on days 1 and 4 of each treatment period. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT), Stroop and Sternberg memory scanning tests. Subjective feelings of sleep and sedation were measured by the Leeds Sleep Evaluation Questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic profiles were determined from analyses of blood samples taken after the final dose on day 5. 4. Overall, there were few changes in any of the psychometric tests and although the higher doses of litoxetine improved CFF, these effects were weak in that differences could only be detected when the results were pooled against time. 5. The pharmacokinetic profile of litoxetine was very similar in both the young and middle aged subjects, and there was no difference regarding tolerability. 6. There is little evidence from this study to suggest that litoxetine has any intrinsic sedative activity which is likely to interfere with the performance of activities of everyday life.

Lack of interaction between two antihistamines, mizolastine and cetirizine, and ethanol in psychomotor and driving performance in healthy subjects.

The pharmacodynamic interaction between mizolastine, a new H1 antihistamine, and ethanol was assessed in a randomized, double-blind, three-way crossover, placebo-controlled study. Eighteen healthy young male volunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo once daily for 7 days with a 1-week wash-out interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on days 5 or 7 of each treatment period, was administered to achieve a peak blood alcohol concentration (BAC) of 0.7 g/l then maintained for 1 h by two further doses of ethanol. Driving ability and psychomotor performance were evaluated using actual and simulated driving tests, critical flicker fusion threshold (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction time of 80 ms, in driving test and DAT performance of + 3.2; and a decrease in CFF and in tracking speed of 2.6 m.s-1. Neither mizolastine nor cetirizine significantly impaired driving ability or arousal (CFF) compared with the placebo. However, both drugs significantly impaired DAT performance 6:00 h post-dose (increase of + 2.1 for mizolastine and + 2.4 for cetirizine). The tracking speed was significantly decreased 7:50 h after mizolastine administration (-1.3 m.s-1) and more consistently from 1:30 to 7:50 h after cetirizine administration (-1.4 m.s-1). No significant adverse interaction, i.e. potentiation, occurred between ethanol and either antihistamine.(ABSTRACT TRUNCATED AT 250 WORDS)

The psychomotor and cognitive effects of a new antihistamine, mizolastine, compared to terfenadine, triprolidine and placebo in healthy volunteers.

Eighteen healthy volunteers received mizolastine 5 mg, 15 mg or 45 mg, terfenadine 60 mg, triprolidine 10 mg or placebo in a 6-way crossover, double blind study. Following each dose, subjects performed a series of tests of cognitive function and psychomotor performance at 1, 3, 5, 8 and 24 hours post-dose. The test battery included critical flicker fusion, choice reaction time, tracking, Stroop and Sternberg memory tests and assessment of subjective sedation. Sedative effects and a concomitant reduction in psychomotor and cognitive function were observed following triprolidine, terfenadine and the highest dose of mizolastine, 45 mg, e.g. triprolidine reduced CFF threshold by 1.5 Hz and increased reaction time by 50 ms, impairments comparable to those caused by blood alcohol concentrations of 50 mg%, the legal limit in many countries. Mizolastine 5 mg did not differ significantly from placebo and at 15 mg differed only at one test point at one time. It may be concluded that mizolastine (5 mg and 15 mg) is free from disruptive effects on cognitive function and psychomotor performance, in contrast to terfenadine 60 mg, triprolidine 10 mg and mizolastine 45 mg.