Flavan-3-gallate catechins in green tea (Camellia sinensis) reduce amiodarone solubility and dissolution in fasted state simulated intestinal fluid

Green tea [ Camellia sinensis (L.) Kuntze] is widely consumed for its cardiovascular benefits, which may overlap with the use of amiodarone, a critical antiarrhythmic drug. Recent in vitro and clinical data indicate that green tea reduced the intestinal solubility and systemic exposure of raloxifene. Raloxifene and amiodarone are both lipophilic drugs that are dependent on solubility for absorption in the intestine. This study investigated the interaction between green tea catechins and amiodarone, focusing on solubility and dissolution in fasted state simulated intestinal fluid. In vitro studies found that green tea extract (GTE) equivalent to 1 cup of brewed tea and the flavan-3-gallate catechin, (−)-epigallocatechin-3-gallate, at an equimolar concentration to that present in the GTE, both significantly decreased soluble amiodarone by 99% and 50%, respectively. In addition, 1 cup of brewed green tea significantly reduced amiodarone dissolution by 74%. In a pharmacokinetic study in fasted mice, GTE did not significantly affect amiodarone’s area under the curve (AUC) and maximum concentration (C max ), which were 15% and 21% lower than controls, respectively. The flavan-3-ol catechin, (−)-epigallocatechin, did not affect amiodarone concentrations in fasted state simulated intestinal fluid or in the mice. A follow-up solubility study found that the vehicle used for liquid gavage in mice contributed to the discrepancy between in vitro and in vivo results. These in vitro findings suggest that green tea consumption may impact the bioavailability of amiodarone, potentially affecting its efficacy; however, further research is needed to explore this interaction in vivo in clinical studies. Amiodarone is a critical antiarrhythmic drug; however, its clinical use can be challenging due to variable bioavailability, raising safety and efficacy concerns. Green tea is often used to improve cardiovascular health. We investigated the potential pharmacokinetic interaction between green tea and amiodarone, examining how green tea catechins may reduce the solubility of amiodarone in the intestine. These findings may have implications for patients who consume green tea alongside amiodarone.