Effects of green tea extract and (?)-epigallocatechin-3-gallate on pharmacokinetics of nadolol in rats |
| |
| Institution: | 1. Department of Pharmacology, School of Medicine, Fukushima Medical University, Fukushima, Japan;2. Department of Hygiene and Preventive Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan;3. Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan;1. Department of Pharmacy, Radboud University Medical Center, Nijmegen 6500 HB, Netherlands;1. Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan;2. Department of Cardiology and Nephrology, Mie University School of Medicine, Tsu, Mie, Japan;3. Department of Gastroenterology and Hepatology, Mie University School of Medicine, Tsu, Mie, Japan;1. Department of Pharmacology, University of Pécs, Faculty of Pharmacy, Szigeti út 12, Pécs H-7624, Hungary;2. János Szentágothai Research Center, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary;3. Department of Pharmacognosy, University of Pécs, Faculty of Pharmacy, Rókus utca 2, Pécs H-7624, Hungary;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, Rókus utca 2, H-7624 Pécs, Hungary;1. Institute of Chemical Kinetics and Combustion, Institutskaya St., 3, 630090 Novosibirsk, Russia;2. Novosibirsk State University, Novosibirsk, Russia;3. Institute of Solid State Chemistry and Mechanochemistry, Novosibirsk, Russia |
| |
| 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. |
| |
| Keywords: | (?)-Epigallocatechin-3-gallate Food–drug interaction Green tea extract Nadolol Pharmacokinetics |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
