A 4-week, multicenter, duodenal ulcer healing trial comparing four escalating doses of ranitidine.

In a randomized double-blind 4-wk trial, ranitidine doses of 300 mg at bedtime (hs), twice daily (bid), three times daily (tid), and four times daily (qid) were compared in 629 patients with endoscopically confirmed duodenal ulcer(s). Endoscopies were performed at baseline and after 4 wk of therapy. Per protocol analysis revealed wk 4 healing rates that were significantly increased (p < or = 0.001) for the bid, tid, and qid groups, compared with the hs group. All treatments provided early symptomatic (ulcer pain) relief. No significant differences in adverse events or laboratory abnormalities were observed between groups. Ranitidine 300 mg bid provides an alternative therapeutic approach for patient populations at risk for ulcer complications. These patients include those with the following: a past history of an upper gastrointestinal hemorrhage, perforation, obstruction, penetration, or giant (> 2.0 cm) duodenal ulcer. The elderly and those with chronic unresponsive ulcerations may also be included in this population.

Paradoxical bronchospasm after use of inhalation aerosols: a review of the literature.

Various formulations of beta-agonists and other bronchodilators have been associated with unexpected bronchoconstriction in certain individuals. Even though the number of affected individuals represents a relatively small percentage and the etiologies may differ among patients, it is important for the public to be aware of the potential for paradoxical bronchospasm and for the physician to investigate each case accordingly.

Relative bioavailability of a controlled-release albuterol formulation for twice-daily use.

A two-way-crossover bioavailability study was completed with 15 healthy male volunteers to evaluate the relative bioavailability of an orally administered controlled-release (CR) formulation of albuterol as compared to the immediate-release (IR) formulation of albuterol. The CR formulation of albuterol used in this study was based mechanistically on the elementary osmotic pump. Each subject received one 8 mg CR tablet every 12 h for 8 consecutive days and one 4 mg IR tablet every 6 h for 8 consecutive days, with 7 days separating each phase. During day 8 of dosing, hourly blood samples (0-12 h) were collected after the morning dose and three additional samples were obtained 16, 20 and 24 h following this dose. Plasma concentrations were measured using a gas chromatography-mass spectrometry procedure. No statistically significant differences were observed in mean steady-state values for Cmax, Cmin, AUC(0-12 h) and peak-to-trough fluctuations (PTF) in comparing the two dosage formulations. Mean steady state Tmax values were 2.6 and 6.0 h for the TR and CR formulations, respectively. It was concluded that twice daily administration of the controlled-release formulation of albuterol provides an alternative to four times daily administration of conventional (immediate-release) albuterol tablets.

Beclomethasone dipropionate aqueous nasal spray for seasonal allergic rhinitis in children.

A 3-week double-blind, parallel group study comparing the effectiveness and safety of an aqueous formulation of beclomethasone dipropionate (BDP-AQ) versus placebo was undertaken in 101 patients. Children aged 5 to 13 years with a diagnosis of seasonal allergic rhinitis received one spray in each nostril twice daily of either BDP-AQ (42 micrograms/spray) or an identical placebo spray. Patient assessment at the end of treatment indicated statistically significant improvement in nasal symptoms for BDP-AQ patients. The physicians overall evaluation of treatment indicated that the BDP-AQ-treated patients experienced significantly greater (P = .012) improvement as compared with placebo-treated patients. There was no difference in the incidence of adverse events between the two treatments. The results demonstrate the effectiveness and safety of BDP-AQ nasal spray in the treatment of seasonal allergic rhinitis in children.

Long-term, double-blind comparison of controlled-release albuterol versus sustained-release theophylline in adolescents and adults with asthma.

This parallel-group study compared the safety and efficacy of controlled-release albuterol versus sustained-release theophylline, both administered every 12 hours. One hundred twenty-four adolescent and adult patients with asthma and with chronic reversible obstructive airway disease were studied. All patients qualified with an FEV1 less than or equal to 80% of predicted (not receiving treatment) and greater than or equal to 15% reversibility in FEV1 or greater than or equal to 25% reversibility in FEF25-75% after inhaled isoproterenol. All patients were known to be able to take theophylline without unacceptable adverse effects. Theophylline was titrated for patients to receive, unblinded, theophylline serum concentrations of 10 to 20 micrograms/ml. With subsequent randomization, 62 patients continued to receive theophylline and 62 patients started taking albuterol in the 12-week, double-blind, double-dummy portion of the study. Pulmonary function was measured during a pretreatment visit (unmedicated) and serial assessment was made starting just before the morning dose and continuing for 12 hours after the dose at the end of 1, 6, and 12 weeks of treatment. Both treatment groups exhibited statistically significant increases in FEV1 from the pretreatment visit to all times of observation at weeks 1, 6, and 12. The increases in FEV1 were not significantly different between albuterol and theophylline administration. There was no evidence of tolerance to the bronchodilatory effect during 12 weeks in either treatment group. Only one patient in the study stopped treatment because of an adverse effect. This patient had tremor during albuterol administration. All other adverse events were tolerated or resolved during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosolized beclomethasone in chronic bronchitis. Improved pulmonary function and diminished airway inflammation.

Chronic bronchitis is associated with airways obstruction and inflammation. In order to determine whether aerosolized beclomethasone can modulate airway inflammation and diminish airway obstruction, subjects with chronic bronchitis performed spirometry and underwent bronchoalveolar lavage (BAL) before and after receiving 6 wk of therapy (five puffs four times a day) with either aerosolized beclomethasone (n = 20) or placebo (n = 10) in a double-blinded, randomized fashion. All subjects received aerosolized albuterol before each use of the study medications. Before BAL, the airways were visually assessed for the appearance of inflammation and assigned a score, the bronchitis index. BAL was performed by instilling five 20-ml aliquots of saline into each of three sites and pooling and separately analyzing the returns from the first aliquots to yield a "bronchial sample." The bronchial lavages were repeated in an additional three sites to increase the volume of fluid available for analysis. The fluid was prepared for cytologic examination by cytocentrifugation. Albumin (as a measure of epithelium permeability) and lactoferrin and lysozyme (as measures of serous cell activity) were measured in unconcentrated BAL fluid by enzyme-linked immunosorbent assay, and concentrations in epithelial lining fluid were estimated using urea as an internal marker for dilution. After treatment, the beclomethasone group, but not the placebo group, showed improvement in FVC (p = 0.02), FEV1 (p = 0.002), and 25 to 75% forced expiratory flow (p = 0.006). Associated with the improvement in spirometry, the bronchitis index fell (13.5 +/- 1.0 versus 10.75 +/- 1.1, p = 0.02) in the beclomethasone-treated group, but not the placebo-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)