Effects of phenytoin and carbamazepine on calcium transport in Caco-2 cells

Toxicol In Vitro. 2007 Aug;21(5):855-62. doi: 10.1016/j.tiv.2007.02.008. Epub 2007 Feb 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / pharmacology
  • Anticonvulsants / pharmacology*
  • Biological Transport, Active / drug effects
  • Bone Diseases / chemically induced
  • Caco-2 Cells
  • Calcium / metabolism*
  • Carbamazepine / pharmacology*
  • Cell Membrane Permeability / drug effects
  • Cyclohexanecarboxylic Acids / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fructose / analogs & derivatives
  • Fructose / pharmacology
  • Gabapentin
  • Humans
  • Phenytoin / pharmacology*
  • Topiramate
  • Vitamin D / pharmacology
  • gamma-Aminobutyric Acid / pharmacology


  • Amines
  • Anticonvulsants
  • Cyclohexanecarboxylic Acids
  • Topiramate
  • Vitamin D
  • Fructose
  • Carbamazepine
  • gamma-Aminobutyric Acid
  • Phenytoin
  • Gabapentin
  • Calcium