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 journalArticle

16 Citations (Scopus)

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

Fingerprint

Cytochrome P-450 CYP3A
Simvastatin
Tea
Troleandomycin
Pharmacokinetics
Midazolam
simvastatin acid
Hydroxylation
Microsomes
Cytochrome P-450 Enzyme System
Liver
Inhibitory Concentration 50

Keywords

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

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmaceutical Science

Cite this

Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats. / Misaka, Shingen; Kawabe, Keisuke; Onoue, Satomi; Werba, José Pablo; Giroli, Monica; Watanabe, Hiroshi; Yamada, Shizuo.

In: Drug Metabolism and Pharmacokinetics, Vol. 28, No. 6, 2013, p. 514-518.

Research output: Contribution to journalArticle

Misaka, Shingen ; Kawabe, Keisuke ; Onoue, Satomi ; Werba, José Pablo ; Giroli, Monica ; Watanabe, Hiroshi ; Yamada, Shizuo. / Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats. In: Drug Metabolism and Pharmacokinetics. 2013 ; Vol. 28, No. 6. pp. 514-518.
@article{1b4a35c332274495ae80d3176197cd1e,
title = "Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats",
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.",
keywords = "CYP3A, Green tea extract, Midazolam, Pharmacokinetics, Rat, Simvastatin",
author = "Shingen Misaka and Keisuke Kawabe and Satomi Onoue and Werba, {Jos{\'e} Pablo} and Monica Giroli and Hiroshi Watanabe and Shizuo Yamada",
year = "2013",
doi = "10.2133/dmpk.DMPK-13-NT-006",
language = "English",
volume = "28",
pages = "514--518",
journal = "Drug Metabolism and Pharmacokinetics",
issn = "1347-4367",
publisher = "Japanese Society for the Study of Xenobiotics",
number = "6",

}

TY - JOUR

T1 - Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats

AU - Misaka, Shingen

AU - Kawabe, Keisuke

AU - Onoue, Satomi

AU - Werba, José Pablo

AU - Giroli, Monica

AU - Watanabe, Hiroshi

AU - Yamada, Shizuo

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - CYP3A

KW - Green tea extract

KW - Midazolam

KW - Pharmacokinetics

KW - Rat

KW - Simvastatin

UR - http://www.scopus.com/inward/record.url?scp=84892983485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892983485&partnerID=8YFLogxK

U2 - 10.2133/dmpk.DMPK-13-NT-006

DO - 10.2133/dmpk.DMPK-13-NT-006

M3 - Article

VL - 28

SP - 514

EP - 518

JO - Drug Metabolism and Pharmacokinetics

JF - Drug Metabolism and Pharmacokinetics

SN - 1347-4367

IS - 6

ER -