Green Tea Ingestion Greatly Reduces Plasma Concentrations of Nadolol in Healthy Subjects

Abstract

This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the β-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 μmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.

Effects of β-Blockers and Tricyclic Antidepressants on the Activity of Human Organic Anion Transporting Polypeptide 1A2 (OATP1A2)

“…Rosuvastatin has a high affinity for OATP transporters, as its K m was determined to be 2.6, 4.0, 9.8, and 2.4 mM for OATP1A2, OATP1B1, OATP1B3, and OATP2B1, respectively (Ho et al, 2006). Finally, OATP1A2 is inhibited by various flavonoids, such as naringin, apigenin, kaempferol, quercetin, and several flavonoids found in green tea Mandery et al, 2010;Roth et al, 2011;Misaka et al, 2014). Flavonoids are found in vegetables, fruits, and plants; thus, pharmacokinetic studies using flavonoids focused on intestinal interactions.…”

“…Bailey et al (2007) have demonstrated that ingestion of fexofenadine and a solution of naringin decreased fexofenadine maximum plasma concentration (C max ) and the area under the plasma concentration time curve (AUC). Misaka et al (2014) have shown that green tea decreased nadolol C max and AUC. These interactions assume that OATP1A2 is an intestinal uptake transporter in the human intestine.…”

Green Tea Catechins -Pharmacokinetic Properties and Health Beneficial Effects

“…Individual variation in C max and AUC of catechins after ingestion of green tea extract was observed in our pharmacokinetic study, which may be associated with the variation of P-gp activity among the subjects [26]. Recently, Misaka et al reported a significant catechin-drug interaction; green tea ingestion greatly reduced plasma concentration of β-blocker nadolol mediated by organic anion-transporter OATP1A2 [27]. The catechindrug interaction competitive antagonism or direct inhibition for transporters should be kept in mind in the clinical field.…”

Inhibition of Human Aldehyde Oxidase Activity by Diet-Derived Constituents: Structural Influence, Enzyme-Ligand Interactions, and Clinical Relevance

“…The interaction risk of the red wine component resveratrol, marketed as a supplement with potential as a cancer chemopreventative agent, was predicted to be moderate to high if ingested at "therapeutic" doses (0.5-5 g). EGCG and ECG, two major constituents in green tea, were predicted to have high and moderate interaction risk, respectively, if consumed as tea (Misaka et al, 2014) or a supplement (Chow et al, 2001). These a C max values were limited to studies of healthy volunteers, from whose plasma the parent constituent was measured directly (i.e., independently from any of the metabolites).…”