Clinical Pharmacokinetics

, Volume 25, Issue 6, pp 450–482 | Cite as

Pharmacokinetic Drug Interactions with Antimicrobial Agents

  • J. Gregory Gillum
  • Debra S. Israel
  • Ron E. Polk
Review Article Pharmacokinetic Drug Interactions

Summary

As new classes of antimicrobial drugs have become available, and new uses found for older drugs, pharmacokinetic drug interactions with antimicrobials have become more common. Macrolides, fluoroquinolones, rifamycins, azoles and other agents can interact adversely with commonly used drugs, usually by altering their hepatic metabolism. The mechanisms by which antimicrobial agents alter the biotransformation of other drugs is increasingly understood to reflect inhibition or induction of specific cytochrome P450 enzymes.

Macrolides inhibit cytochrome P450IIIA4 (CYP3A4), which appears to be the most common metabolic enzyme in the human liver and is involved in the metabolism of many drugs, including cyclosporin, warfarin and terfenadine. Some quinolones preferentially inhibit CYP1A2, which is partially responsible for methylxanthine metabolism. Azoles appear to be broad spectrum inhibitors of cytochromes P450. Within each of these antibiotic classes, there is a rank order of inhibitory potency towards specific cytochrome P450 enzymes. By contrast, rifampicin (rifampin) and rifabutin induce several cytochromes P450, including CYP3A4, and hence can enhance the metabolism of many other drugs.

By using in vitro preparations of human enzymes it is increasingly possible to predict those antibiotics that will adversely affect the metabolism of other drugs. In addition, between-patient variability in frequency of interaction may relate to differences in the activities of these enzymes. Although the mechanisms and scope of these interactions are becoming well characterised, the remaining challenge is how to best inform the clinician so that the undesirable consequences of interactions may be prevented.

Keywords

Theophylline Clinical Pharmacology Fluconazole Zidovudine Itraconazole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • J. Gregory Gillum
    • 1
  • Debra S. Israel
    • 1
  • Ron E. Polk
    • 1
  1. 1.School of PharmacyVirginia Commonwealth University, Medical College of VirginiaRichmondUSA

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