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Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats.
Phytomedicine 2013; 20(14):1247-50P

Abstract

Green tea catechins have been shown to affect the activities of drug transporters in vitro, including P-glycoprotein and organic anion transporting polypeptides. However, it remains unclear whether catechins influence the in vivo disposition of substrate drugs for these transporters. In the present study, we investigated effects of green tea extract (GTE) and (-)-epigallocatechin-3-gallate (EGCG) on pharmacokinetics of a non-selective hydrophilic β-blocker nadolol, which is reported to be a substrate for several drug transporters and is not metabolized by cytochrome P450 enzymes. Male Sprague-Dawley rats received GTE (400 mg/kg), EGCG (150 mg/kg) or saline (control) by oral gavage, 30 min before a single intragastric administration of 10 mg/kg nadolol. Plasma and urinary concentrations of nadolol were determined using high performance liquid chromatography. Pharmacokinetic parameters were estimated by a noncompartmental analysis. Pretreatment with GTE resulted in marked reductions in the maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) of nadolol by 85% and 74%, respectively, as compared with control. In addition, EGCG alone significantly reduced Cmax and AUC of nadolol. Amounts of nadolol excreted into the urine were decreased by pretreatments with GTE and EGCG, while the terminal half-life of nadolol was not different among groups. These results suggest that the coadministration with green tea catechins, particularly EGCG, causes a significant alteration in the pharmacokinetics of nadolol, possibly through the inhibition of its intestinal absorption mediated by uptake transporters.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan. Electronic address: misaka@fmu.ac.jp.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23920278

Citation

Misaka, S, et al. "Effects of Green Tea Extract and (-)-epigallocatechin-3-gallate On Pharmacokinetics of Nadolol in Rats." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 20, no. 14, 2013, pp. 1247-50.
Misaka S, Miyazaki N, Fukushima T, et al. Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats. Phytomedicine. 2013;20(14):1247-50.
Misaka, S., Miyazaki, N., Fukushima, T., Yamada, S., & Kimura, J. (2013). Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 20(14), pp. 1247-50. doi:10.1016/j.phymed.2013.07.003.
Misaka S, et al. Effects of Green Tea Extract and (-)-epigallocatechin-3-gallate On Pharmacokinetics of Nadolol in Rats. Phytomedicine. 2013 Nov 15;20(14):1247-50. PubMed PMID: 23920278.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of green tea extract and (-)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats. AU - Misaka,S, AU - Miyazaki,N, AU - Fukushima,T, AU - Yamada,S, AU - Kimura,J, Y1 - 2013/08/03/ PY - 2013/02/25/received PY - 2013/05/16/revised PY - 2013/07/02/accepted PY - 2013/8/8/entrez PY - 2013/8/8/pubmed PY - 2014/5/9/medline KW - (−)-Epigallocatechin-3-gallate KW - (−)-epigallocatechin-3-gallate KW - AUC KW - BCS KW - BDDCS KW - CYP KW - EGCG KW - Food–drug interaction KW - GTE KW - Green tea extract KW - Nadolol KW - OATP KW - P-glycoprotein KW - P-gp KW - Pharmacokinetics KW - area under the time–plasma concentration curve KW - biopharmaceutical classification system KW - biopharmaceutics drug disposition classification system KW - cytochrome P450 KW - green tea extract KW - organic anion transporting polypeptide SP - 1247 EP - 50 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 20 IS - 14 N2 - Green tea catechins have been shown to affect the activities of drug transporters in vitro, including P-glycoprotein and organic anion transporting polypeptides. However, it remains unclear whether catechins influence the in vivo disposition of substrate drugs for these transporters. In the present study, we investigated effects of green tea extract (GTE) and (-)-epigallocatechin-3-gallate (EGCG) on pharmacokinetics of a non-selective hydrophilic β-blocker nadolol, which is reported to be a substrate for several drug transporters and is not metabolized by cytochrome P450 enzymes. Male Sprague-Dawley rats received GTE (400 mg/kg), EGCG (150 mg/kg) or saline (control) by oral gavage, 30 min before a single intragastric administration of 10 mg/kg nadolol. Plasma and urinary concentrations of nadolol were determined using high performance liquid chromatography. Pharmacokinetic parameters were estimated by a noncompartmental analysis. Pretreatment with GTE resulted in marked reductions in the maximum concentration (Cmax) and area under the time-plasma concentration curve (AUC) of nadolol by 85% and 74%, respectively, as compared with control. In addition, EGCG alone significantly reduced Cmax and AUC of nadolol. Amounts of nadolol excreted into the urine were decreased by pretreatments with GTE and EGCG, while the terminal half-life of nadolol was not different among groups. These results suggest that the coadministration with green tea catechins, particularly EGCG, causes a significant alteration in the pharmacokinetics of nadolol, possibly through the inhibition of its intestinal absorption mediated by uptake transporters. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/23920278/Effects_of_green_tea_extract_and_____epigallocatechin_3_gallate_on_pharmacokinetics_of_nadolol_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(13)00247-X DB - PRIME DP - Unbound Medicine ER -