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Effects of uptake and efflux transporter inhibition on erythromycin breath test results

L A Frassetto1, S Poon, C Tsourounis

  • 1Clinical Research Center and Department of Medicine, University of California at San Francisco, San Francisco, CA, USA. Leslie.Benet@ucsf.edu

Clinical Pharmacology and Therapeutics
|March 16, 2007
PubMed

Insights

The erythromycin breath test (EBT) may inaccurately reflect CYP3A4 metabolism due to transporter interactions. Rifampin and lansoprazole significantly altered EBT results, highlighting the need to consider transporter effects in drug metabolism studies.

Area of Science:

  • Pharmacokinetics
  • Drug Metabolism
  • Biomarker Development

Background:

  • The erythromycin breath test (EBT) is widely used to assess CYP3A4 enzyme activity.
  • CYP3A4 is a major drug-metabolizing enzyme, and its activity is crucial for drug efficacy and safety.
  • Potential confounding factors, such as drug transporters, may influence EBT results.

Purpose of the Study:

  • To investigate whether changes in EBT results are influenced by drug transporters, specifically P-glycoprotein (P-gp) and organic anion transporting polypeptides (OATPs).
  • To determine the impact of lansoprazole (a P-gp inhibitor) and rifampin (an OATP inhibitor) on EBT measurements of CYP3A4 activity.

Main Methods:

  • Three EBT tests were performed on healthy adults: baseline, with lansoprazole, and with rifampin.
  • Respiratory (14)C excretion was measured to quantify CYP3A4 activity.
  • Statistical analysis was used to compare EBT results under different drug treatment conditions.

Main Results:

  • Rifampin significantly decreased (14)C excretion, while lansoprazole showed a trend towards increasing it, compared to baseline.
  • A significant difference in (14)C excretion was observed between lansoprazole and rifampin treatments.
  • Sex-specific differences were noted, with women exhibiting significant changes in (14)C excretion following both rifampin and lansoprazole administration.

Conclusions:

  • EBT results can be significantly affected by the inhibition of drug transporters like P-gp and OATPs.
  • Relying solely on EBT without accounting for transporter interactions may lead to misinterpretation of CYP3A4 metabolic activity.
  • Future studies should consider the role of drug transporters when using EBT to evaluate CYP3A4 function.

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