The nasty surprise of a complex drug-drug interaction

Drug Discov Today. 2010 May;15(9-10):391-5. doi: 10.1016/j.drudis.2010.02.013. Epub 2010 Mar 6.

Abstract

In vitro investigation of pharmacokinetic drug-drug interactions (DDIs) has officially been part of the regulatory pathway for new drugs in the USA since the publication of an FDA guidance on the subject in 1997. The field has continued to evolve, driven by preclinical and clinical experience, improved understanding of the molecular basis of DDIs, technological advances, and a continuous dialogue between the FDA and pharmaceutical industry scientists. Some striking DDIs involve multiple molecular species and targets; their mechanisms and magnitude would have been difficult or impossible to predict with available in vitro tools. This article focuses on one such example.

Publication types

  • Review

MeSH terms

  • Carbamates / adverse effects*
  • Carbamates / pharmacokinetics
  • Drug Approval
  • Drug Evaluation, Preclinical / methods*
  • Drug Industry / methods
  • Drug Interactions*
  • Drug Therapy, Combination / adverse effects*
  • Gemfibrozil / adverse effects*
  • Gemfibrozil / pharmacokinetics
  • Humans
  • Itraconazole / adverse effects*
  • Itraconazole / pharmacokinetics
  • Models, Biological
  • Piperidines / adverse effects*
  • Piperidines / pharmacokinetics

Substances

  • Carbamates
  • Piperidines
  • Itraconazole
  • repaglinide
  • Gemfibrozil