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Design and Validation of a Volumetric-extrusion Bioprinter for Bioprinting of Soluble Basement Membrane Extract for Translational Research
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Brandon T Gufford1, Ingrid F Metzger2, Nadia O Bamfo3

  • 1Covance, Inc., United States.

The Journal of Pharmacology and Experimental Therapeutics
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PubMed
Summary
This summary is machine-generated.

Efavirenz (an antiretroviral) acutely inhibits but chronically induces CYP2B6 activity, affecting bupropion metabolism differently over time. These drug-drug interactions are dependent on CYP2B6 genotype.

Keywords:
CYP inductionCYP inhibitionDrug interactionsclearanceclinical pharmacologydrug disposition

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Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Genetics

Background:

  • Efavirenz is a key antiretroviral medication.
  • CYP2B6 genotype influences drug metabolism.
  • Bupropion (BUP) is metabolized by CYP2B6.

Purpose of the Study:

  • To investigate efavirenz's acute and chronic effects on bupropion disposition.
  • To determine the role of CYP2B6 genotypes in efavirenz-bupropion drug-drug interactions (DDIs).

Main Methods:

  • A three-phase, open-label study in 53 healthy volunteers.
  • Administration of bupropion alone, with acute efavirenz, and after chronic efavirenz.
  • Analysis of bupropion and its active metabolites' exposure.

Main Results:

  • Efavirenz acutely decreased, and chronically increased, hydroxybupropion exposure.
  • Chronic efavirenz enhanced elimination of bupropion and its metabolites.
  • Interactions were dependent on CYP2B6 genotype and non-stereospecific.

Conclusions:

  • Efavirenz exhibits time- and CYP2B6 genotype-dependent inhibition and induction of CYP2B6.
  • Findings have implications for bupropion safety, efficacy, and personalized therapy.
  • Novel mechanisms of efavirenz-bupropion DDIs were elucidated.