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A single dose of clorazepate 20 mg was injected i.m. in 7 pregnant and 7 non-pregnant women. Blood samples were collected for one week, and urine was collected for 24 h after the dose. The concentrations of clorazepate and its metabolite nordiazepam were determined by electron capture gas liquid chromatography. There was no difference between the two groups on physical examinations. Clorazepate was rapidly absorbed and the peak concentration was reached within 2 h. Mean pharmacokinetic parameters for clorazepate were absorption half life 0.77 h in pregnant women and 0.56 h in non-pregnant women; elimination half life 1.3 h in pregnant women and 2.0 h in non-pregnant women; volume of distribution: 0.43 1 . kg-1 in the pregnant women and 0.33 1 . kg-1 in non-pregnant women. Nordiazepam reached its peak concentration within 12 h after dosing; its mean half life of elimination was 180 h in pregnant women and 60 h in non-pregnant women. Within 24 h, 1.3% of the clorazepate was recovered in urine from pregnant women and 7% in urine from the non-pregnant women.

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 1) 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 12 agonist appears not to be influenced by either steroid in these patients.