The efficacy of ketotifen in a controlled double-blind food challenge study in patients with food allergy.

The effectiveness of oral ketotifen was compared with that of placebo in 26 patients with food allergy in a randomized, double-blind parallel study. Patients were selected on the basis of food allergy as established by history, clinical improvement after an exclusion diet, and reappearance of the symptoms after a challenge with the food. Thirteen patients were given ketotifen and 13, placebo. Ketotifen or placebo were administered twice daily for 1 month after the first oral provocation test and the last dose was given 12 hours before the second oral provocation test. Ketotifen protected patients (7/13) significantly more than placebo (2/13; P less than .05). The results of this study suggest that ketotifen may be useful for some patients with food allergy.

Effects of pindolol and metoprolol on plasma lipids and lipoproteins.

1 The effects of two beta-adrenoceptor blocking drugs, pindolol and metoprolol, on plasma lipids and lipoproteins were studied in sixteen hypertensive patients (WHO I-I) by a cross-over design, with two active treatment periods of 12 weeks each. 2 Neither pindolol nor metoprolol had any effect on total plasma cholesterol (total-C), triglycerides (TG) or low-density lipoprotein cholesterol (LDL-C). 3 Pindolol significantly increased high-density lipoprotein cholesterol (HDL-C). After metoprolol, HDL-C levels remained similar to those in the placebo period. 4 The ratio of total-C to HDL-C was significantly reduced by pindolol only. 5 Compared with the placebo period, both pindolol and metoprolol significantly reduced heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure. The decreases in HR were significantly greater after metoprolol. No differences between the effects of the two drugs on SBP and/or DBP were observed.

A comparison between inhaled clenbuterol and salbutamol in chronic bronchitis with reversible airway obstruction.

Twenty-one patients with chronic bronchitis and reversible airway obstruction participated in two single-blind, cross-over, placebo-controlled studies in inhaled clenbuterol - a new bronchodilator - and salbutamol. Nine patients participated in a dose-response study. Clenbuterol 10 microgram/puff, salbutamol 100 microgram/puff and placebo, were given by pressurized aerosol in cumulative doses of 1, 2, 4, 8, and 16 inhalations of each drug and placebo. The mean peak % FEV1 increases above the baseline were similar after all doses of clenbuterol and salbutamol and were significantly greater than after placebo. No cardiovascular effects were observed. Tremors were noted in two patients after 160 microgram clenbuterol and in one patient after 1600 microgram salbutamol. In a second study, clenbuterol (20 microgram), salbutamol (200 microgram) - two equieffective doses - and placebo were compared in a 6 h period in 12 patients. Clenbuterol and salbutamol produced bronchodilation of comparable magnitude, onset of action (15 min) and duration (4-6 h). Clenbuterol is an effective bronchodilator and, on the basis of molecular weight, about ten times more potent than salbutamol when given by aerosol.

A clinical trial of oral clenbuterol (NAB 365) in chronic airways obstruction.

A new oral bronchodilator, clenbuterol, was compared with terbutaline during a 5-week single-blind crossover study in 16 patients with chronic airways obstruction and with cough and sputum production. After a run-in period (1 week), the study was performed in two separated 2-week periods (Phase II and Phase IV), separated by a 1-week drug-free period. Oral clenbuterol was administered at 20 to 30 micrograms 3-times daily, oral terbutaline at 2.5 to 5 mg 3-times daily. The forced expiratory volume in 1 second (FEV1) was measured at the beginning and end of Phase II and Phase IV under baseline conditions, and 1 hour after an oral dose of clenbuterol or terbutaline. Parents recorded subjective and objective information in a daily diary and used no bronchidilator therapy for 12 hours before each visit. Clenbuterol and terbutaline significantly improved baseline FEV1 and the bronchodilator effects of single oral doses were similar. The mean dyspnoea, cough and sputum score values after treatments were lower than during the wash-out period (p less than 0.05). Tremors were noted in 6 patients on clenbuterol and 5 on terbutaline. It is suggested that clenbuterol is a good alternative oral drug for treatment of chronic airways obstruction.

Oral NAB 365 (clenbuterol) and terbutaline in chronic obstructive lung disease: a double-blind, two-week study.

The bronchodilator effects of large oral doses of clenbuterol (30 micrograms, t.i.d.) and terbutaline sulfate (5 mg, t.i.d.) were compared using the forced expiratory volume in one second (FEV1), the specific airway resistance (sRaw) and the maximum expiratory flow at 50% of vital capacity (V50% VC) in a double-blind, two-week study, with groups of 12 patients each. The patients suffered from chronic obstructive lung disease with partially reversible airway obstruction. The bronchodilator actions of the two medications were significant between 30 and 240 minutes after the first administration on day 1 and between 30 and 60 minutes after the first administration on day 14. The administration of hydroxyphenylorciprenaline at 60 min on day 14 produced a significant additional bronchodilating effect over the bronchodilating effects of clenbuterol and terbutaline. The basal values recorded on days 7 and 14 demonstrated a significant improvement of pulmonary function over the basal values on day 1, similar in both groups. No tachyphylaxis to the bronchodilator effect to either drug occurred over the two-week study period. Neither the incidence nor the nature of side effects differed in the two treated groups. No changes in heart rate or blood pressure were noted. No abnormal effects on blood gas tension or laboratory results were observed. It was concluded that oral clenbuterol is about 170 times more potent than oral terbutaline.

Intravenous NAB 365 (clenbuterol) and terbutaline in exercise-induced bronchospasm (EIB).

In a single-blind, placebo-controlled, cross-over study, the effects of intravenous 20 micrograms NAB 365 (clenbuterol) and intravenous 250 microgram terbutaline were compared in nine asthmatic patients with bronchospasm induced by exercise. The exercise consisted of treadmill running. The two beta-adrenergic bronchodilator drugs effectively prevented post-exercise bronchospasm in eight of the nine patients. The effects were superior to those in the untreated group and in the placebo-treated group. Six of the patients treated with terbutaline complained of adverse reactions (tremor, palpitation, tachycardia). No adverse reactions were observed after clenbuterol.

NAB 365 (clenbuterol) and salbutamol in asthmatics: a double-blind clinical trial.

A double-blind comparison between orally administered NAB 365 (clenbuterol) and salbutamol was conducted in 30 impatients with either asthma or chronic bronchitis with asthma who had at least 15% reversibility in airway obstruction following inhalation of 1,500 microgram of orciprenaline. NAB 365 (clenbuterol) was administered to 15 patients at 30 microgram b.i.d. for 3 days; then the dosage was reduced to 20 microgram b.i.d. Salbutamol was administered to the other 15 patients at 4 mg t.i.d. Both drugs were administered for an average of 13 days. NAB 365 (clenbuterol) was shown to be an effective bronchodilator, with more rapid activity than that of salbutamol, on the FVC, FEV1, PEFR, the differences being significant on the third and seventh day of treatment. These findings are briefly discussed. No significant cardiovascular effects were noted for either drug, nor were differences found in need for additional treatment or in side-effects.

Aerosolized clenbuterol (NAB 365) and salbutamol in exercise-induced asthma.

The effect of clenbuterol (NAB 365) in inhibiting exercise-induced asthma was compared with that of salbutamol in a single-blind, placebo-controlled, crossover study. Single doses of 20 microgram clenbuterol and 200 microgram salbutamol were given by inhalation 180 minutes before exercise to 9 patients. The exercise used was treadmill running. Clenbuterol offered complete protection to 7 patients, partial protection to 1 and no protection to 1 patient. Salbutamol offered complete protection to 5 patients, partial protection to 1 and no protection to 3 patients. One patient was not protected by any treatment. The protective effects of the two beta-adrenergic bronchodilator drugs were similar (p = 0.42 for FEV1 and p = 0.10 for FEF25-75%). Placebo failed to prevent exercised-induced asthma in any patient. No adverse reactions were manifested or reported by the patients.

Pirenzepine (LS 519) in severe duodenal ulcer and in gastric ulcer. A double-blind clinical trial.

Duodenal ulcer. Forty-five of 49 adult outpatients with active, severe, endoscopically proven duodenal ulcers completed a 4-week double-blind trial comparing two doses of LS 519 (75 and 150 mg/day) with placebo. After 2 weeks, 1 of 15 patients given LS 75 mg and 4 of 15 given LS 150 mg/day had healed (P = 0.09). No patient given placebo had healed. After 4 weeks, 6 of 15 (40%) on placebo, 9 of 15 (60%) on LS 75 mg and 13 of 15 (86.7%) on LS 153 mg had healed (P less than 0.01). Patients given the highest dose of LS had significantly more pain-free days and nights and took fewer antacid tablets than those receiving the lowest dose of LS or placebo. Gastric ulcer. 19 of 20 adult outpatients with endoscopically proven active benign gastric ulcers completed a double-blind 4-week trial with either LS 519 (75 mg/day) or carbenoxolone (300 mg/day). Six of 10 (60%) given LS and 6 of 9 (66.7%) given carbenoxolone had healed after 4 weeks (N.S.). Symptomatic improvement was significantly faster in the LS group than in the carbenoxolone group. Hypokaliemia, increases in alkaline phosphatase and SGOT were observed in the carbenoxolone group.

Dose-response study of a new oral bronchodilator, NAB 365 (clenbuterol).

A new oral bronchodilator, NAB 365 (clenbuterol), at doses of 10, 20, 30 and 40 microgram, was studied in a double-blind placebo-controlled incomplete cross-over study in 10 patients suffering from chronic bronchitis who had reversible airway obstruction. The ventilatory response was assessed by measurement of the forced expiratory volume in 1 sec (FEV1), total airway resistance (Raw) and specific airway conductance (sGaw) before and 30, 60, 120, 180, 240, 360 and 480 min after administration. With the 30 and 40 microgram doses, a significant bronchodilating effect was seen between 30 and 360 min after administration, with peak effects between 120 and 240 min. The maximal effects in ventilatory response after 30 microg were only slightly less than after 40 microgram; the bronchodilating effect of 20 microgram was statistically less marked than those of 30 of 30 and 40 microgram on FEV1, but not statistically different on Raw and sGaw. These findings have been briefly discussed. The effects of 10 microgram and of the placebo were always statistically lower than those of 20 microgram. No significant cardiovascular effects and no subjective side effects were observed. In conclusion, the results suggest that 30 microgram of NAB 365 (clenbuterol) are the suitable acute dose.

Relative potency of the atropine-like effects of a new parasympatholytic drug, scopolamine-N-(cyclopropyl methyl) bromide and those of hyoscine-N-butyl bromide.

A double-blind crossover trial with a 4-point bioassay was carried out in 8 convalescent in-patients to study the relative potency of scopolamine-N-(cyclopropyl methyl) bromide (DA 3177), a new parasympatholytic drug, administered at doses of 2.5 mg and 5 mg i.v., and hyoscine-N-butyl bromide, administered at doses of 10 mg and 20 mg i.v., in producing atropine-like effects. The results showed that the effects on heart rate and near point of accommodation were slightly less with DA 3177, while its effects on salivary secretion were a little greater than those of hyoscine-N-butyl bromide. It is suggested that study of the pharmacodynamic effects of parasympatholytic drugs is a relatively simple way of predicting which doses should be effective spasmolytically.