Polyvalent cations in the gastrointestinal tract

Polyvalent cations in the gastrointestinal tract refer to a group of multivalent metal ions, such as calcium (Ca2+), magnesium (Mg2+), aluminum (Al3+), and iron (Fe2+/Fe3+), that play a pivotal role in the pharmacokinetics of numerous oral medications [1, 2]. These ions are prevalent in the gut due to dietary intake (e.g., dairy products), mineral supplements, and common over-the-counter products like antacids and laxatives [11, 18]. From a pharmacological perspective, they act as targets for chelation, where they form stable, insoluble complexes with drugs including fluoroquinolone and tetracycline antibiotics, bisphosphonates, and HIV integrase inhibitors [3, 4, 14]. This complexation prevents the drug from being absorbed across the intestinal epithelium, leading to significantly reduced systemic exposure and potential therapeutic failure [5, 6]. Beyond their role in drug interactions, polyvalent cations like lanthanum and calcium are therapeutically employed as phosphate binders to treat hyperphosphatemia in chronic kidney disease by sequestering dietary phosphate in the gut [7, 10]. Understanding the behavior of these cations is essential for optimizing drug delivery and avoiding clinically significant drug-nutrient or drug-drug interactions [1, 11].

Other names

Multivalent cationsDivalent and trivalent cationsChelating cationsDietary mineralsMetal ions

Chelation and formation of insoluble, non-absorbable complexes in the gastrointestinal lumen, which significantly reduces the bioavailability of co-administered medications.