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  11. Deconvoluting Zavegepant Drug-drug Interactions: A Phase I Study To Evaluate The Effects Of Rifampin And Itraconazole On Zavegepant Pharmacokinetics.
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  3. Research Domains
  5. Engineering
  7. Environmental Engineering
  9. Air Pollution Modelling And Control
  11. Deconvoluting Zavegepant Drug-drug Interactions: A Phase I Study To Evaluate The Effects Of Rifampin And Itraconazole On Zavegepant Pharmacokinetics.

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Deconvoluting zavegepant drug-drug interactions: A phase I study to evaluate the effects of rifampin and itraconazole on zavegepant pharmacokinetics.

Rajinder Bhardwaj1, Jo Ann Malatesta1, Jennifer Madonia2

  • 1Certara USA, Princeton, New Jersey, USA.

Clinical and Translational Science
|November 27, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

This study investigated drug interactions with zavegepant, a migraine treatment. Itraconazole had minimal effect on nasal zavegepant but increased oral zavegepant exposure, while rifampin significantly increased oral zavegepant levels.

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Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Clinical Pharmacology

Background:

  • Zavegepant is a calcitonin gene-related peptide receptor antagonist for acute migraine.
  • Understanding drug-drug interactions is crucial for safe and effective migraine treatment.

Purpose of the Study:

  • To evaluate the pharmacokinetic interactions of intranasal/oral zavegepant with itraconazole (CYP3A4/P-gp inhibitor).
  • To assess the pharmacokinetic interactions of oral zavegepant with rifampin (CYP3A4/P-gp inducer and OATP1B3 inhibitor).

Main Methods:

  • Phase I, open-label, fixed-sequence study in healthy participants.
  • Two cohorts: zavegepant with itraconazole, and oral zavegepant with rifampin.
  • Pharmacokinetic parameters (AUC, Cmax) of zavegepant were measured.

Main Results:

  • Itraconazole did not significantly alter intranasal zavegepant exposure.
  • Oral zavegepant exposure increased by 59% (AUC) and 77% (Cmax) with itraconazole.
  • Oral zavegepant exposure increased approximately 2.3-fold (AUC) and 2.2-fold (Cmax) with rifampin.

Conclusions:

  • OATP1B3 and intestinal P-gp are key players in zavegepant drug-drug interactions, more so than CYP3A4.
  • Avoid coadministration of OATP1B3 inhibitors with intranasal zavegepant.