Pharmacokinetic Assessment of Atazanavir and Favipiravir Following <i>Echinacea</i> Supplementation: A Controlled Herb–Drug Interaction Investigation

ABSTRACT Echinacea is a widely used herbal supplement and is frequently co‐administered with antiviral drugs, raising concerns regarding potential herb–drug interactions. This study evaluated the effect of repeated Echinacea administration on the pharmacokinetics of favipiravir and atazanavir in rats. Male Sprague Dawley rats were administered Echinacea (250 mg/kg) or vehicle once daily for 10 days, followed by a single oral dose of favipiravir (70 mg/kg) or atazanavir (35 mg/kg). Plasma drug concentrations were quantified using validated LC–MS/MS methods, and pharmacokinetic parameters were determined by noncompartmental analysis. Echinacea co‐administration did not significantly alter favipiravir exposure ( C max : 39,677 ± 5385 vs. 36,364 ± 5379 ng/mL; AUC0–t: 144,457 ± 17,267 vs. 104,840 ± 27,001 ng h/mL) or atazanavir exposure ( C max : 3274 ± 256 vs. 4004 ± 629 ng/mL; AUC0–t: 8962 ± 1667 vs. 10,645 ± 2949 ng h/mL). No relevant changes were observed in clearance, half‐life, or mean residence time for either drug. These findings indicate that repeated Echinacea administration does not result in a pharmacokinetically relevant interaction with favipiravir or atazanavir under the investigated conditions.