Effects of Tea Polyphenols on the Pharmacokinetics of Atorvastatin and Underlying Mechanisms in Hyperlipidemic Rats

ABSTRACT

This study systematically explored the impact of tea polyphenol (TP) on the pharmacokinetics of atorvastatin (ATV) and underlying mechanisms in male Sprague–Dawley rats with hyperlipidemia induced by high‐fat diet. The study was conducted using UHPLC–MS/MS, Western Blot, and in situ single‐pass intestinal perfusion experiments. Pharmacokinetic analysis revealed that high‐dose TP administration (200 mg/kg, 7 days) significantly reduced the C _max and AUC _{0– t} of ATV by 43.83% and 43.38%, respectively, while increasing CL _z / F by 85.04%. Similar reductions were observed for statin metabolites 2‐hydroxy atorvastatin (o‐ATV) and 4‐hydroxy atorvastatin (ρ‐ATV). Western blot results showed that 7‐day TP treatment downregulated CYP3A4 expression but upregulated intestinal P‐gp expression to 1.37‐fold (LDTP) and 1.84‐fold (HDTP). Intestinal perfusion experiments further confirmed that TP decreased the cumulative intestinal absorption amount ( M ) of ATV by 40%. EGCG and ECG exhibited significant inhibitory effects to ATV intestinal absorption, reducing the M by 44% and 48%, respectively. In contrast, EGC and EC showed a nonsignificant trend toward slightly increased absorption of ATV. In summary, TP may lower ATV bioavailability through P‐gp‐mediated efflux induction and potential physicochemical interactions, implying caution for long‐term high‐dose intake of TP or supplements.