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CGP 51901 is a non-anaphylactogenic mouse/human chimeric anti-human IgE antibody that binds to free IgE and surface IgE of IgE-expressing B cells but not to IgE bound to high affinity IgE receptors (Fc epsilonR1) on mast cells and basophils or low affinity IgE receptors (Fc epsilonR2) on other cells. A phase 1 double-blind, placebo-controlled, single dose study with doses of 3, 10, 30, and 100 mg of CGP 51901 was conducted in 33 pollen-sensitive subjects who had raised levels of serum IgE and received either intravenous CGP 51901 or placebo. The administration of CGP 51901 was well tolerated and resulted in a decrease of serum free IgE levels in a dose-dependent manner, with suppression after 100 mg of CGP 51901 reaching > 96%. Time of recovery to 50% of baseline IgE correlated with the dose of administered antibody and ranged from a mean of 1.3 d for the 3 mg to 39 d for the 100 mg dose. Total IgE, comprised of free and complexed IgE, increased as stored and newly synthesized IgE bound to CGP 51901. Complexed IgE was eliminated at a rate comparable with the terminal half-life of free CGP 51901 (11-13 d at all doses). Only one subject showed a weak antibody response against CGP 51901. We conclude that the use of anti-human IgE antibody is safe and effective in reducing serum IgE levels in atopic individuals and provides a potential therapeutic approach to the treatment of atopic diseases.

The objective of this study was to evaluate the potency and efficacy (intrinsic activity) of formoterol and salmeterol and their duration of action in comparison with other beta-adrenoceptor agonists in isolated human bronchi. Human bronchi were obtained at thoracotomy from patients with lung cancer. Potency (-log of the concentration of drug inducing 50% of maximal relaxation (-log EC50)) and efficacy (maximal effect (Emax), % of response to theophylline 3 x 10(-3) mol.l-1) were determined by analysis of cumulative isometric concentration-response curves to beta 2-adrenoceptor agonists in bronchial rings at resting tone or contracted maximally with acetylcholine 10(-3) mol.l-1 to induce functional antagonism. The onset and duration of action of beta-adrenoceptor agonists were measured by assessing the relaxant activity of drugs on the basal tone of isolated bronchi. In terms of potency, the rank order of the substances studied was formoterol > fenoterol > or = salmeterol > or = isoprenaline > or = salbutamol > or = adrenaline > or = terbutaline. Formoterol was 150-200 times more potent than isoprenaline. On preparations contracted with acetylcholine 10(-3) mol.l-1 the intrinsic activity (IA) of salbutamol, terbutaline and salmeterol compared with that of isoprenaline ranged 0.62-0.66. Intrinsic activity was higher with formoterol (0.84) and fenoterol (0.75). The onset of action of formoterol (2.14 +/- 0.55 min, n = 11) was not significantly different from that of salbutamol (1.90 +/- 0.24 min, n = 8) but shorter than that of salmeterol (6.40 +/- 1.40 min, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)

Twelve patients with chronic severe asthma, having previously shown an FEV1 increase of less than 20% of the predicted value with prednisolone treatment (20-60 mg daily for 10 days), took part in a double blind crossover comparison of equipotent anti-inflammatory doses of betamethasone and prednisolone. Betamethasone (8 mg) and prednisolone (40 mg) were administered daily for 10 days with a washout period of 10 days between. In this first part of the study betamethasone was administered intramuscularly and prednisolone orally. Placebo injections and tablets were used. Mean FEV1 was not significantly different before each period. There was a significant increase in FEV1 while they were taking betamethasone but not prednisolone. Individual analysis of the data showed that FEV1 increased with betamethasone in nine patients and remained stable or decreased in three. During treatment with prednisolone baseline FEV1 increased moderately in three patients (FEV1 0.3, 0.5 and 0.6 l) and remained stable or decreased in nine. There was no significant difference between the bronchodilator responses to cumulative doses of inhaled salbutamol when they were measured immediately before, on the last day of treatment with each steroid, and between steroid treatment periods. The same protocol was followed four months later in five of the 12 patients but both drugs were administered orally on this occasion. Similar results were obtained. The greater effect of betamethasone on bronchial obstruction may be due to its longer biological half life or to some unidentified property of its metabolites. The bronchial response to inhaled beta 2 agonist appears not to be influenced by either steroid in these patients.