Ketoconazole and other imidazole derivatives are potent inhibitors of peroxisomal phytanic acid alpha-oxidation

FEBS Lett. 1995 Dec 18;377(2):213-6. doi: 10.1016/0014-5793(95)01341-5.


The imidazole antimycotics like ketoconazole, clotrimazole, bifonazole, miconazole and CO, known as powerful inhibitors of cytochrome P-450, are potent inhibitors of peroxisomal phytanic acid alpha-oxidation to pristanic acid suggesting the possible involvement of the cytochrome P-450 mono-oxygenase system in this oxidation. In contrast to the inhibition of the oxidation of [1-14C]phytanic acid, [1-14C]phytanoyl-CoA and [(2,3)-3H]phytanic acid, these drugs and CO have no effect on the oxidation of [1-14C]alpha-hydroxy phytanic acid indicating that these drugs and CO inhibit only the alpha-hydroxylation of phytanic acid. These studies using purified peroxisomes from liver and cultured human skin fibroblasts and Hep G2 cells clearly demonstrate that alpha-hydroxylation, an intermediate step in the alpha-oxidation of phytanic acid found to be impaired in Refsum Disease, is mediated by cytochrome P-450 containing enzyme.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbon Monoxide / pharmacology
  • Humans
  • Imidazoles / pharmacology*
  • Ketoconazole / pharmacology*
  • Microbodies / drug effects
  • Oxidation-Reduction
  • Phytanic Acid / antagonists & inhibitors*


  • Imidazoles
  • Phytanic Acid
  • Carbon Monoxide
  • Ketoconazole