In vitro study of the inhibition and induction of human cytochromes P450 by crystalline glucosamine sulfate

Stefano Persiani, Luca Canciani, Patrice Larger, Roberto Rotini, Giovanni Trisolino, Diego Antonioli, Lucio C. Rovati

Research output: Contribution to journalArticle

Abstract

The induction and inhibition of human hepatic cytochrome P450 (CYP) isoforms by crystalline glucosamine sulfate (CGS) was investigated in vitro. Inhibition of CYP1A2, CYP2E1, CYP2C19, CYP2C9, CYP2D6, and CYP3A4 by CGS was assessed using recombinant human enzymes incubated with CGS (up to 3 mM expressed as free base). Induction of CYP1A2, CYP2B6, CYP2C9, CYP2C19 and CYP3A4 by CGS (0.01, 0.3 and 3 mM) was evaluated in cryo-preserved human hepatocytes, by determining CYP mRNA expression using quantitative RT-PCR. CGS produced no inhibition or induction of any the CYP enzymes tested at concentrations hundred folds higher than the steady state peak plasma concentrations (approximately 10 μM) observed in man after therapeutic doses of CGS of 1,500 mg once a day. Therefore, no clinically relevant metabolic interactions are expected between CGS and co-administered drugs that are substrates of the CYP enzymes investigated.

Original languageEnglish
Pages (from-to)195-209
Number of pages15
JournalDrug Metabolism and Drug Interactions
Volume24
Issue number2-4
Publication statusPublished - 2009

Keywords

  • Crystalline glucosamine sulfate
  • Drug-drug interactions
  • Human P450 induction
  • Human P450 inhibition

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'In vitro study of the inhibition and induction of human cytochromes P450 by crystalline glucosamine sulfate'. Together they form a unique fingerprint.

  • Cite this