Effect of Sucralfate on Phenytoin Bioavailability

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 $173.6\pm 22.6\frac{\text{mg}•\text{h}}{\text{L}}\text{to}157.1\pm 19.6\frac{\text{mg}•\text{h}}{\text{L}}\left(\text{p}\<0.02\right)$ , and the phenytoin AUC₁₂₀ was reduced from 200.5 ± $31.9\frac{\text{mg}•\text{h}}{\text{L}}\text{to}185.0\pm 26.8\frac{\text{mg}•\text{h}}{\text{L}}\left(\text{p}\<0.05\right)$ , 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.