Direct effects of diphenylhydantoin (phenytoin) on the ion-transporting ATPases of cultured osteoblast-like cells.

Diphenylhydantoin (phenytoin) added to cultures of osteoblast-like cells at a concentration of 10 microM, at the high end of the therapeutic range in plasma of unbound phenytoin (4-8 microM), caused reductions in Na+, K+-ATPase and alkaline phosphatase activities and increases in Ca2+-ATPase and HCO3--ATPase activities in homogenates of whole cells and in subcellular fractions of cultured osteoblast-like cells. These data suggest that, if these changes occur in vivo, the osteomalacia associated with treatment with diphenylhydantoin may be mediated in part by direct effects on the ability of bone cells to transport ions.