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Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
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Drug interactions during therapy with three major groups of antimicrobial agents

Kasra Shakeri-Nejad1, Ralf Stahlmann

  • 1PAREXEL International GmbH, Institute of Clinical Pharmacology, Clinical Operations, Spandauer Damm 130, Haus 18, 14050 Berlin, Germany.

Expert Opinion on Pharmacotherapy
|March 25, 2006
PubMed

Insights

Antimicrobial drugs like macrolides and azoles can cause drug interactions by inhibiting CYP enzymes. Quinolones may have reduced absorption with mineral supplements, affecting treatment efficacy.

Area of Science:

  • Pharmacology
  • Microbiology
  • Drug Interactions

Background:

  • Antimicrobial agents are crucial for treating bacterial and fungal infections.
  • Understanding drug-drug interactions (DDIs) is vital for safe and effective patient care.
  • Macrolides, quinolones, and azoles are common antimicrobial classes with potential for DDIs.

Purpose of the Study:

  • To review drug-drug interactions associated with macrolides, quinolones, and azoles.
  • To elucidate the mechanisms behind these interactions.
  • To inform clinical practice regarding concurrent administration of these antimicrobials.

Main Methods:

  • Literature review of studies on drug interactions involving macrolides, quinolones, and azoles.
  • Analysis of pharmacokinetic and pharmacodynamic data related to these drug classes.
  • Identification of specific enzymes and transporters involved in DDIs.

Main Results:

  • Macrolides and ketolides inhibit CYP3A4, affecting metabolism of numerous drugs.
  • Azithromycin, unlike other macrolides, does not inhibit cytochrome enzymes.
  • Quinolones can chelate with cations, reducing absorption; ciprofloxacin inhibits CYP1A2, impacting theophylline metabolism.
  • Systemic azoles inhibit various CYP isoenzymes (CYP3A4, CYP2C9, CYP2C19) and can be substrates of P-glycoprotein, leading to complex interactions.

Conclusions:

  • Macrolides, quinolones, and azoles exhibit distinct drug interaction profiles.
  • Inhibition of CYP enzymes and cation chelation are key mechanisms for macrolide and quinolone interactions.
  • Azole antifungals present significant interaction potential due to broad CYP inhibition and P-glycoprotein interactions, especially in polypharmacy settings.

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