Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats

Shingen Misaka, Keisuke Kawabe, Satomi Onoue, José Pablo Werba, Monica Giroli, Hiroshi Watanabe, Shizuo Yamada

Research output: Contribution to journalArticlepeer-review

Abstract

Summary: Effects of green tea extract (GTE) on the activity of cytochrome P450 (CYP) enzymes and pharmacokinetics of simvastatin (SIM) were investigated in rats. Inhibitory effects of GTE on CYP3A activity were investigated in rat hepatic microsomes (RHM) using midazolam (MDZ) 1′-hydroxylation as a probe reaction. SD female rats received a single oral dose of GTE (400mg/kg) or troleandomycin (TAO, a CYP3A selective inhibitor, 500mg/kg), followed 30min later by SIM (20mg/kg). Plasma concentrations of SIM and its active metabolite, simvastatin acid, were determined up to 6 h after the SIM administration using LC/MS/MS. In RHM, GTE inhibited MDZ 1′-hydroxylation with IC50 and Ki app values of 12.5 and 18.8 μg/mL, respectively, in a noncompetitive manner. Area under plasma concentration-time curves for SIM in the GTE and TAO groups were increased by 3.4- and 10.2-fold, respectively, compared with the control. The maximum concentrations of SIM were higher in the GTE (3.3-fold) and TAO (9.5-fold) groups. GTE alters the pharmacokinetics of SIM, probably by inhibiting intestinal CYP3A.

Original languageEnglish
Pages (from-to)514-518
Number of pages5
JournalDrug Metabolism and Pharmacokinetics
Volume28
Issue number6
DOIs
Publication statusPublished - 2013

Keywords

  • CYP3A
  • Green tea extract
  • Midazolam
  • Pharmacokinetics
  • Rat
  • Simvastatin

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmaceutical Science

Fingerprint

Dive into the research topics of 'Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats'. Together they form a unique fingerprint.

Cite this