No abstract

Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000-mg sucralfate tablets between 8 AM and 10 PM one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two-day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration-time curves before and after sucralfate (mean +/- SD) were 496.0 +/- 80.9 and 770.9 +/- 146.6 hr-ng/mL, respectively. This increase is statistically significant (P less than .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.

The mechanism of action of the antiulcer agent, sucralfate, involves drug binding to proteins, pepsin, and bile salts. The potential for sucralfate to bind to, and inhibit the oral absorption of, concurrently-administered drugs has been studied for very few agents. Phenytoin bioavailability was studied following a single dose of phenytoin 500 mg po in nine normal subjects during a control period and when given with sucralfate. Area under the serum concentration-time curve was compared at 48 hours (AUC48) and 120 hours (AUC120) using observed and extrapolated data. The phenytoin AUC48 was reduced from 173.6 +/- 22.6 mg . h/L to 157.1 +/- 19.6 mg . h/L (p less than 0.02), and the phenytoin AUC120 was reduced from 200.5 +/- 31.9 mg . h/L to 185.0 +/- 26.8 mg . h/L (p less than 0.05), when sucralfate was administered. Because AUC comparisons for drugs with nonlinear elimination kinetics may reflect changes in rate, as well as extent, of absorption, these small changes in AUC may not reflect a change in the fraction of dose absorbed. However, our results suggest that sucralfate does affect phenytoin absorption. Further studies may be useful in determining the precise nature and clinical importance of this interaction.

No abstract

The objective of this study was to examine the effectiveness of inhaled beclomethasone in the treatment of stable chronic obstructive airway disease (COAD). Eight patients completed a randomized, double-blind, placebo-controlled, crossover trial of inhaled beclomethasone and oral prednisone. Each patient received 3 treatment regimens given for 14 days: inhaled beclomethasone, prednisone, and placebo. There were no statistically significant differences in pulmonary function tests, oxygen cost diagram, or 12-minute walking distance test among the regimens. The only improvement in arterial blood gasses was partial pressure of oxygen, which was negligibly increased during prednisone treatment compared with beclomethasone and with placebo (p less than 0.05). Evaluation of 95% confidence intervals indicated that clinically significant mean differences were unlikely with either beclomethasone or prednisone. Larger studies are required to determine if a responsive subgroup exists, and to determine if this form of therapy has a role in treatment of COAD.