Factors determining the oral absorption and systemic disposition of zeaxanthin in rats: in vitro , in situ , and in vivo evaluations

Abstract

Context Zeaxanthin is a yellow‑coloured dietary carotenoid widely recognized as an essential component of the macula. It exerts blue light filtering and antioxidant activities, offering eye health and vision benefits. Objective This study explores the oral absorption and systemic disposition of zeaxanthin from biopharmaceutical and pharmacokinetic perspectives. Materials and methods In vivo intravenous (5 and 10 mg/kg) and intraportal (5 mg/kg) pharmacokinetic studies were performed to determine intrinsic tissue‑blood partition coefficient, elimination pathway, and hepatic clearance, of zeaxanthin in rats. Moreover, in vitro physicochemical property test, in situ closed loop study, in vivo oral pharmacokinetic study (20 and 100 mg/kg), and in vivo lymphatic absorption study (100 mg/kg) were conducted to investigate the gut absorption properties of zeaxanthin and assess the effects of several lipids on the lymphatic absorption of zeaxanthin in rats. Results Zeaxanthin exhibited poor solubility (≤144 ng/mL) and stability (6.0–76.9% of the initial amount remained at 24 h) in simulated gut luminal fluids. Gut absorption of zeaxanthin occurred primarily in the duodenum, but the major fraction (≥84.7%) of the dose remained unabsorbed across the entire gut tract. Considerable fractions of intravenous zeaxanthin accumulated in the liver, lung, and spleen (21.3, 11.7, and 2.0%, respectively). It was found that the liver is the major eliminating organ of zeaxanthin, accounting for 53.5–90.1% of the total clearance process (hepatic extraction ratio of 0.623). Discussion and conclusions To our knowledge, this is the first systematic study to report factors that determine the oral bioavailability and systemic clearance of zeaxanthin.

A High-Performance Liquid Chromatography with Photodiode Array Detection Method for Simultaneous Determination of Three Compounds Isolated from Wikstroemia ganpi: Assessment of the Effects on Cytochrome P450-Mediated Metabolism In Vitro and In Vivo

“…Several factors might have contributed to these findings. One of the causes may be low bioavailability due to chemical degradation of phytochemicals and the intestinal/hepatic first pass [ 38 , 41 , 49 , 50 ], and plasma and liver concentrations of inhibitors may be insufficient for the IC 50 obtained in vitro CYP inhibition studies [ 51 , 52 ]. Consequently, a single oral dose of WGM did not have significant effects on the pharmacokinetics of buspirone in rats, suggesting that WGM cannot function as an inhibitor of CYP3A-mediated metabolism in vivo.…”

“…To evaluate the effects of WGM on the pharmacokinetics of BUS in vivo, 12 rats underwent surgical cannulation of the femoral artery after anesthetization via an intramuscular injection of 10 mg/kg zoletil [ 40 , 41 ]. After sufficient recovery from anesthesia, 6 rats were administered a single oral dose of BUS (30 mg/kg) and 6 rats were administered WGM (1 g/kg) together with BUS.…”

Lutein-Rich Beverage Alleviates Visual Fatigue in the Hyperglycemia Model of Sprague–Dawley Rats

“…The occurrence of visual fatigue is related to ocular muscle fatigue, eye dryness, retinal dysfunction, and other factors. Recent studies have shown that oxidative stress is also closely related to the occurrence of visual fatigue [25,26].…”