Clinical Drug–Drug Pharmacokinetic Interaction Potential of Sucralfate with Other Drugs: Review and Perspectives

Abstract

Sucralfate, a complex of aluminium hydroxide with sulfated sucrose, forms a strong gastrointestinal tract (GIT) mucosal barrier with excellent anti-ulcer property. Because sucralfate does not undergo any significant oral absorption, sucralfate resides in the GIT for a considerable length of time. The unabsorbed sucralfate may alter the pharmacokinetics of the oral drugs by impeding its absorption and reducing the oral bioavailability. Because of the increased use of sucralfate, it was important to provide a reappraisal of the published clinical drug-drug interaction studies of sucralfate with scores of drugs. This review covers several category of drugs such as non-steroidal anti-inflammatory drugs, fluoroquinolones, histamine H2-receptor blockers, macrolides, anti-fungals, anti-diabetics, salicylic acid derivatives, steroidal anti-inflammatory drugs and provides pharmacokinetic data summary along with study design, objectives and key remarks. While the loss of oral bioavailability was significant for the fluoroquinolone class, it generally varied for other classes of drugs, suggesting that impact of the co-administration of sucralfate is manageable in clinical situations. Given the technology advancement in formulation development, it may be in order feasible to develop appropriate formulation strategies to either avoid or minimize the absorption-related issues when co-administered with sucralfate. It is recommended that consideration of both in vitro and preclinical studies may be in order to gauge the level of interaction of a drug with sucralfate. Such data may aid in the development of appropriate strategies to navigate the co-administration of sucralfate with other drugs in this age of polypharmacy.

The influence of feeding and gastroprotectant medications on the Factor Xa inhibitory activity of orally administered rivaroxaban in normal dogs

“…Sucralfate, another commonly prescribed gastroprotectant, is a complex of sulfated sucrose and aluminum 16,17 . It protects the gastrointestinal mucosal barrier from gastric acid damage by providing a physical barrier, as well as increasing local bicarbonate production to buffer its effects.…”

“…Historically, there have been concerns about the coadministration of gastroprotectants with antithrombotics, particularly omeprazole with clopidogrel 15 . In addition, sucralfate, a complex of aluminum hydroxide with sulfated sucrose, has strong gastrointestinal mucosal barrier properties and could interfere with the absorption of other orally administered drugs including antithrombotics 16,17 …”

Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses

“…Sucralfate is another common class of drug co-administered with NSAIDs for its gastroprotective effects. Sucralfate is thought to have multiple mechanisms of action, including mucosal synthesis, formation of a protective mucosal barrier, buffering of hydrogen ions and encouraging luminal secretion of PGE 2 leading to increased epithelial cell restitution [ 77 ]. Pharmacokinetic studies investigating the drug interaction between sucralfate and NSAIDs in humans suggest that co-administration of the drugs may lead to delayed absorption of NSAIDs, however no studies investigating drug interaction on pharmacokinetic parameters in horses have been published [ 77 ].…”

Topical sucralfate for treatment of mucocutaneous conditions: A systematic review on clinical evidences

“…Uncontrolled diabetes, advanced kidney diseases, and sensitivity to the drug are the only contraindications for its use. 1,[3][4][5] Even though exact sucralfate in-vivo mechanisms of action remain unknown, in-vitro studies have suggested the seven following mechanisms: 1. inhibition of bacterial activity; 2. reducing oxygen-free radical generation; 3. the effects on arachidonic acid metabolism and increasing prostaglandin release by activating macrophages, cyclooxygenase activity, synthesis, and release of leukotriene C4; 4. decreasing cell apoptosis; 5. enhancing growth factor bioavailability; 6. the effects as a site-protective agent through providing a physical barrier; 7. the effects on tissue growth, regeneration, and repair: facilitating blood flow, cell proliferation, and repair via binding growth factors to tissues 6,7 (Figure 1). In addition to systemic sucralfate, a topical form of drug efficacy has been evaluated in several mucocutaneous indications as clinical and case studies.…”