title: Effects of phenytoin and carbamazepine on calcium transport in Caco-2 cells.
abstract: Adverse effects of anti-seizure/anti-epileptic medications on bone density have been observed and reported since the early 1960s. Phenytoin and carbamazepine are two commonly prescribed anti-epileptic drugs most frequently associated with osteomalacia including fractures, bone demineralization, and reduced bone formation. The mechanism by which anti-epileptic drugs induce bone loss is not fully explained. We hypothesized that anti-epileptic drugs may impair dietary calcium absorption in the intestine. Using Caco-2 cells, a model transport system for study of the function of the intestinal epithelium, we determined the effects of several anti-epileptic drugs on intestinal epithelial calcium transport. In our system, phenytoin and carbamazepine dose-dependently inhibit active calcium transport from the apical to basolateral side of Caco-2 cells under physiologic calcium conditions. Vitamin D ameliorates the anti-epileptic drug-induced decrease in calcium permeability.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97330, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: von Borstel Smith
authors.forename: Kristi
authors.initials: K
authors.lastname: Crofoot
authors.forename: Rosita
authors.initials: R
authors.lastname: Rodriguez-Proteau
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Filtz
mesh_terms: D000588:Amines / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D001847:Bone Diseases / Q000139:chemically induced; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism*; D002220:Carbamazepine / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D000077206:Gabapentin; D006801:Humans; D010672:Phenytoin / Q000494:pharmacology*; D000077236:Topiramate; D014807:Vitamin D / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D000077236:Topiramate; D014807:Vitamin D; D005632:Fructose; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin; D002118:Calcium