Evaluation of induction potency of new drug candidates on CYP1A2 and CYP3A4 using real-time one-step RT-PCR in primary cultures of cryopreserved human hepatocytes

Masuhiro Nishimura, Shizuo Narimatsu, Shinsaku Naito

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

This study evaluates the induction potency of new drug candidates on mRNA levels of CYP1A2 and CYP3A4 in primary cultures of cryopreserved human hepatocytes. Analysis was performed by quantita- tive real-time RT-PCR using primers and TaqMan probes. Positive controls for CYP1A2 and CYP3A4 used β-naphthoflavone (β-NF) and rifampicin (Rif), respectively. In the first stage of the study, the lot showing the best induction of mRNA expression CYP1A2 and CYP3A4 from among eight lots of hepatocytes was select- ed. In the second stage, we evaluated the levels of CYP1A2 and CYP3A4 gene expression in hepatocytes af- ter exposure to eight NO-1886 (ibrolipim) derivatives. A combination of real-time one-step RT-PCR and primary culture of cryopreserved human hepatocytes is suitable for evaluating of induction potency of a large number of new drug candidates.

Original languageEnglish
Pages (from-to)446-450
Number of pages5
JournalDrug Metabolism And Pharmacokinetics
Volume24
Issue number5
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • CYP1A2
  • CYP3A4
  • Cryopreserved human hepatocytes
  • New drug candidates
  • Primary cultures
  • mRNA induction

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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