STEREOCHEMICAL ASPECTS OF ITRACONAZOLE METABOLISM IN VITRO AND IN VIVO

@article{Kunze2006STEREOCHEMICALAO,
  title={STEREOCHEMICAL ASPECTS OF ITRACONAZOLE METABOLISM IN VITRO AND IN VIVO},
  author={K. Kunze and W. L. Nelson and E. Kharasch and K. Thummel and N. Isoherranen},
  journal={Drug Metabolism and Disposition},
  year={2006},
  volume={34},
  pages={583 - 590}
}
Itraconazole (ITZ) has three chiral centers and is administered clinically as a mixture of four stereoisomers. This study evaluated stereoselectivity in ITZ metabolism. In vitro experiments were carried out using heterologously expressed CYP3A4. Only (2R,4S,2′R)-ITZ and (2R,4S,2′S)-ITZ were metabolized by CYP3A4 to hydroxy-ITZ, keto-ITZ, and N-desalkyl-ITZ. When (2S,4R,2′R)-ITZ or (2S,4R,2′S)-ITZ was incubated with CYP3A4, neither metabolites nor substrate depletion were detected. Despite these… Expand
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