Absorption characteristics and in vivo behavior of astaxanthin isomers: insights from the administration of highly purified (all-E)-, (9Z)-, and (13Z)-astaxanthin in male mice

Abstract

Astaxanthin, a xanthophyll carotenoid with potent antioxidant properties, exists in multiple geometrical isomers whose differences in bioavailability, in vivo stability, and isomerization behavior remain insufficiently characterized. Here, we conducted a comprehensive comparative analysis of the pharmacokinetics of purified (all-E)-, (9Z)-, and (13Z)-astaxanthin isomers following oral and intravenous administration in ICR male mice. Using both non-compartmental and population pharmacokinetic (PopPK) modeling, we quantified isomer-specific parameters including clearance (CL), bioavailability (F), and absorption lag time (T_lag). Among the isomers, (13Z)-astaxanthin exhibited superior systemic exposure and hepatic accumulation, with markedly lower clearance and higher oral bioavailability than the 9Z- and all-E-isomers. In contrast, (9Z)-astaxanthin demonstrated rapid elimination and extensive in vivo isomerization, possibly associated with enzymatic metabolism during intestinal absorption. Molecular docking simulations revealed stronger binding affinities of (13Z)-astaxanthin to key transport proteins, such as apolipoprotein AI (ApoA-I) and serum albumin (SA), supporting its prolonged systemic retention. These findings not only confirm that geometric isomerism significantly influences the pharmacokinetic behavior of astaxanthin but also reconcile conflicting literature regarding the bioavailability of Z-isomer-rich carotenoids. Importantly, our data underscore the need for isomer-specific formulation strategies and suggest that (13Z)-astaxanthin is a promising candidate for enhanced delivery in nutraceutical and therapeutic applications.