SULCRATE (sucralfate) exerts a generalized gastric cytoprotective effect by enhancing natural mucosal defense mechanisms. Studies conducted in animals and clinical trials in humans have demonstrated that sucralfate can protect the gastric mucosa against various irritants such as alcohol, ASA, hydrochloric acid, sodium hydroxide or sodium taurocholate.
In addition, sucralfate has been demonstrated to have a greater affinity for ulcerated gastric or duodenal mucosa than for nonulcerated mucosa.
Sucralfate produces an adherent and cytoprotective barrier at the ulcer site. This barrier protects the ulcer site from the potential ulcerogenic properties of acid, pepsin and bile. Furthermore, sucralfate blocks acid diffusion across the sucralfate protein barrier and also complexes directly with pepsin and bile.
The action of sucralfate is nonsystemic as the drug is only minimally absorbed from the gastrointestinal tract. The minute amounts of the sulfated disaccharide which are absorbed are primarily excreted in the urine.
Each g of sucralfate contains approximately 200 mg of aluminum. The aluminum moiety can dissociate at low pH and aluminum release in the stomach can be expected; however, aluminum is poorly absorbed from the intact gastrointestinal tract. Following administration of 1 g of sucralfate (tablets or suspension) 4 times a day to individuals with normal renal function, approximately 0.001% to 0.017% of sucralfate's aluminum content is absorbed and excreted in the urine. This results in an aluminum load of between 0.008 mg and 0.136 mg following a 4 g daily dose. Individuals with normal renal function excrete absorbed aluminum and can respond to an increased aluminum load by increasing urinary excretion.
These values were determined in individuals with intact gastrointestinal mucosa. Available evidence does not indicate that absorption of aluminum would be different in individuals with ulcerated gastrointestinal mucosa.
Experiments have shown that sucralfate is not an antacid.
Antacids should not be taken within half an hour before or after sucralfate intake because of the possibility of decreased binding of sucralfate with the gastroduodenal mucosa as a consequence of a change of intragastric pH.
Animal studies have shown that simultaneous administration of sucralfate with tetracycline, phenytoin or cimetidine results in a statistically significant reduction in the bioavailability of these agents. Cimetidine absorption was not reduced in humans.
In clinical trials, the concomitant administration of sucralfate reduced the bioavailability of digoxin. In case of simultaneous administration, the extent of absorption of phenytoin, warfarin and fluoroquinolone antibiotics (e.g. ciprofloxacin and norfloxacin) is also reduced. These interactions appear to be nonsystemic and to result from the binding of sucralfate to the concomitantly administered drug in the gastrointestinal tract. In all cases, complete bioavailability was restored by separating the administration of sucralfate from that of the other agent by 2 hours.
Sucralfate, administered respectively 30 and 60 minutes before ASA or ibuprofen did not alter the bioavailability of these agents. In a study comparing the prior administration of a single dose of sucralfate tablets on the bioavailability of naproxen, indomethacin or ketoprofen versus administration in the absence of sucralfate, it was shown that the total amount of these drugs absorbed was not altered; however, the peak concentration of each was reduced, and the time to reach peak concentration was delayed. A single dose of SULCRATE Suspension Plus administered one-half hour before naproxen had a similar effect on the bioavailability of naproxen.
The physician should consider the possible clinical implications of these interactions. It is recommended to separate the administration of any drug from that of sucralfate when the potential for altered bioavailability is felt to be critical to the effectiveness of that drug.
