Evidence of CYP3A Allosterism In Vivo: Analysis of Interaction Between Fluconazole and Midazolam

  title={Evidence of CYP3A Allosterism In Vivo: Analysis of Interaction Between Fluconazole and Midazolam},
  author={J. Yang and W. Atkins and N. Isoherranen and M. Paine and K. Thummel},
  journal={Clinical Pharmacology & Therapeutics},
  • J. Yang, W. Atkins, +2 authors K. Thummel
  • Published 2012
  • Biology, Medicine
  • Clinical Pharmacology & Therapeutics
  • The allosteric effect of fluconazole (effector) on the formation of 1′–hydroxymidazolam (1′–OH–MDZ) and 4–hydroxymidazolam (4–OH–MDZ) from midazolam (MDZ), a substrate of CYP3A4/5—members of the cytochrome P450 superfamily of enzymes—was examined in healthy volunteers. Following pretreatment with fluconazole, the ratio of the areas under the curve (AUCs) for 4–OH–MDZ and MDZ (AUC4–OH/AUCMDZ) increased by 35–62%, whereas the ratio AUC1′–OH/AUCMDZ decreased by 5–37%; the ratio AUC1′–OH/AUC4–OH… CONTINUE READING
    29 Citations
    Drug Interaction of Efavirenz and Midazolam: Efavirenz Activates the CYP3A-Mediated Midazolam 1′-Hydroxylation In Vitro
    • 22
    • PDF
    Effect of CYP3A5 Expression on the Inhibition of CYP3A-Catalyzed Drug Metabolism: Impact on Modeling CYP3A-Mediated Drug-Drug Interactions
    • 19
    • PDF


    In Vivo CYP3A4 Heteroactivation Is a Possible Mechanism for the Drug Interaction between Felbamate and Carbamazepine
    • 67
    • PDF
    Minimal in vivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone.
    • 42
    Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects
    • 86
    • PDF
    Characterization of 1′-Hydroxymidazolam Glucuronidation in Human Liver Microsomess⃞
    • 48
    • PDF
    In vitro and in vivo glucuronidation of midazolam in humans.
    • 65