Effects of benzodiazepines on laryngeal reflexes

Of 20 volunteers, five were given intravenous Diazemuls 15 mg over 15 seconds, and three groups of five were given lormetazepam 2 mg intravenously over 10, 20 and 60 seconds, respectively. Laryngeal reactivity and psychomotor function were tested at intervals from prior to injection until 4 hours after injection. For equivalent degrees of depression of psychomotor function, lormetazepam depressed the laryngeal reflex less than Diazemuls (p = 0.004). Lormetazepam give over 60 seconds depressed the laryngeal reflex more than when given over 10 seconds (p = 0.008) or over 20 seconds (p = 0.048), although a significant difference was not demonstrated between the 10-second and 20-second groups. These results concur with experimental evidence that benzodiazepine receptor multiplicity exists, which allows various members of the benzodiazepine group of drugs to exhibit differing therapeutic ratios for their various effects.     

Oral lormetazepam in premedication. A comparison with diazepam

Lormetazepam, a relatively new benzodiazepine was compared in a randomised, double blind trial with diazepam for its effectiveness as an oral premedicant drug. A scoring system was used to assess sedation, relief of anxiety, nausea, dizziness and cardiovascular effects in two groups of patients having orthopaedic operations. Some statistical indication that lormetazepam has a greater anxiolytic effect than diazepam was found, but in assessing total effect using a known scoring system, no difference was demonstrated between the two drugs.     

Sublingual lormetazepam in the treatment of sleep disorders in general practice patients

The sublingual form of the benzodiazepine hypnotic lormetazepam was developed with the aim of attaining greater flexibility in the treatment of sleep disorders. The object is to achieve rapid onset of hypnotic effect and provide patients with a form of medication which they can take after having gone to bed and only if they have difficulty in falling asleep. In a placebo-controlled crossover double-blind study the hypnotic effect, side-effects and acceptance of lormetazepam sublingual (1 mg) were investigated in 60 patients with sleep disorders receiving treatment from physicians in independent practices. The study was conducted over a total of 2 weeks, the patients receiving lormetazepam and placebo for 7 days respectively, changing over in the second week. The results show that in the sublingual form lormetazepam (1) is distinctly better than placebo as regards hypnotic efficacy, particularly with respect to the reduction of sleep latency; (2) does not lead to a significantly higher rate of concomitant symptoms than placebo; and (3) is well accepted by the patientsin the wafer form.     

A randomized clinical trial comparing doses and efficacy of lormetazepam tablets or oral solution for insomnia in a general practice setting

Lormetazepam is a short-acting benzodiazepine hypnotic which is beneficial in shortening the time to onset of sleep. The aim of the study was to assess a new formulation of lormetazepam (oral solution) in comparison with lormetazepam tablets in out-patients with insomnia. This trial was an open randomized parallel group study conducted by 30 general practitioners. One hundred and eight patients took 0.5 mg on the first night and were allowed to increase their dosage by 0.25 mg (for oral solution) and 0.5 mg (for tablets), respectively, each day and every 2 days. The patients assessed the efficacy, acceptability and tolerance of lormetazepam using a diary card and a set of visual analogue scales assessing their sleep. Over 14 days of treatment, the mean daily dose of lormetazepam was lower in the oral solution group than in the tablets group (0.78 mg versus 0.97 mg). The cumulated dose of lormetazepam was lower with the oral solution (18% reduction). No significant difference between the two groups was found in the assessment of sleep characteristics. The occurrence of side effects did not differ between the two groups. These results suggest that a unitary dose as achieved by an oral solution of lormetazepam allows easier determination of the minimal individual effective dose.     

Pharmacokinetics and biotransformation of the new benzodiazepine,lormetazepam, in man

Summary The concentrations of lormetazepam and its glucuronide in plasma and milk were determined during administration of 10 daily doses of lormetazepam 2 mg (2 tablets of NOCTAMID^® - 1) to five mothers delivered by Caesarian section. Their babies were breast-fed throughout the study, and the plasma levels of lormetazepam and its glucuronide were determined three times in the babies. At 12 and 24h after administration, the plasma level of lormetazepam was about 3.5 ng/ml and 1.8 ng/ml in mothers, and below 0.09 ng/ml in the children. In milk the lormetazepam concentration was below 0.2 ng/ml. The plasma level of glucuronide varied between 24 ng/ml at 12h and 11 ng/ml 24h after administration. Almost no accumulation of unchanged lormetazepam was observed (factor: 1.3). The ratio of the levels of lormetazepam in milk and plasma was estimated to be below 0.06, and for the glucuronide the ratio was 0.04. The quantity of free and conjugated active ingredient transferred to the children via breast milk was calculated to be at most 100 ng/kg, corresponding to 0.35% of the maternal dose, which is regarded as tolerable.