Exposure of Fexofenadine, but Not Pseudoephedrine, Is Markedly Decreased by Green Tea Extract in Healthy Volunteers

Abstract

Green tea (GT) alters the disposition of a number of drugs, such as nadolol and lisinopril. However, it is unknown whether GT affects disposition of hydrophilic anti-allergic drugs. The purpose of this study was to investigate whether pharmacokinetics of fexofenadine and pseudoephedrine are affected by catechins, major GT components.A randomized, open, 2-phase crossover study was conducted in 10 healthy Japanese volunteers. After overnight fasting, subjects were simultaneously administered fexofenadine (60 mg) and pseudoephedrine (120 mg) with an aqueous solution of green tea extract (GTE) containing (−)-epigallocatechin gallate (EGCG) of ~ 300 mg or water (control). In vitro transport assays were performed using HEK293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated fexofenadine transport. In the GTE phase, the area under the plasma concentration-time curve and the amount excreted unchanged into urine for 24 hours of fexofenadine were significantly decreased by 70% (P < 0.001) and 67% (P < 0.001), respectively, compared with control. There were no differences in time to maximum plasma concentration and the elimination half-life of fexofenadine between phases. Fexofenadine was confirmed to be a substrate of OATP1A2, and EGCG (100 and 1,000 μM) and GTE (0.1 and 1 mg/mL) inhibited OATP1A2-mediated uptake of fexofenadine. On the contrary, the concomitant administration of GTE did not influence the pharmacokinetics of pseudoephedrine. These results suggest that intake of GT may result in a markedly reduced exposure of fexofenadine, but not of pseudoephedrine, putatively by inhibiting OATP1A2-mediated intestinal absorption.

Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications

“…As evidenced by clinical studies, the significant degree of variability in the pharmacokinetic parameters of EGCG might be explained by genetic variations in the genes encoding the drug transporters MRP2 and organic anion transporter SLC21A6 (OATP1B1). It is possible that this interindividual heterogeneity could account for the quantities of green tea polyphenols in human plasma or their potential to induce beneficial effects [ 364 ] and their potential to trigger pharmacokinetic interaction with other drugs [ 365 , 366 , 367 , 368 ].…”

Co‐consuming green tea with raloxifene decreases raloxifene systemic exposure in healthy adult participants

“…Common mechanisms include induction or inhibition of drug metabolizing enzymes, particularly the cytochrome P450s (CYPs), and transporters. Regarding transporters, studies showed green tea to decrease systemic area under the plasma concentration versus time curve (AUC) to the minimally metabolized drugs digoxin, fexofenadine, lisinopril, and nadolol 8–12 . These observations were attributed to inhibition of an intestinal uptake transporter(s) by green tea.…”

“…Regarding transporters, studies showed green tea to decrease systemic area under the plasma concentration versus time curve (AUC) to the minimally metabolized drugs digoxin, fexofenadine, lisinopril, and nadolol. 8 , 9 , 10 , 11 , 12 These observations were attributed to inhibition of an intestinal uptake transporter(s) by green tea. Pharmacokinetic green tea–drug interactions involving biochemical targets in the intestine in addition to the CYPs and transporters, such as UDP‐glucuronosyltransferases (UGTs), remain understudied.…”