Superior Oral Bioavailability in Beagle Dogs of Lutein Derived from a Novel Manufacturing Process
Authors: Sunvold Gregory D. , Brandt Karsten , Ribera David , Lazaar Alain , Wedekind Karen J. , Torras Raquel , Guirado Glòria , Evans Joseph L. , Reznick Gary , Castells Gloria 
Published: November 2023

ObjectiveLutein, an essential micronutrient that plays a critical role in promoting immune health, is being developed commercially (as Lutea® 20) using a novel manufacturing process. Lutea® 20 features reduced lutein crystal size (>99%<0.5 microns) compared to an existing lutein‐containing product, Existing Lutein Product (ELP) (64%<0.5 microns), along with enhanced stability without the requirement for including protective antioxidants. The objective of this study was to compare the oral bioavailability of lutein derived from Lutea® 20 (manufactured using novel technology) to that of lutein derived from ELP (manufactured using traditional technology).MethodsThe study was performed in 12 healthy Beagle dogs [pre‐study mean body weight (bw) of 14.3 ± 2.6 kg)] using a cross‐over, 4 × 4 Latin square design. Each animal was randomly assigned to one sequence group, and 1 of 4 treatments administered by oral gavage during each period, i.e., Lutea® 20 at 2.5 and 5 mg/kg bw and ELP at 2.5 and 5 mg/kg bw. All animals received all the treatments in sequence, with a between‐period wash‐out of 13–15 days. For each period, blood samples were collected from each animal at −24 h (pre‐administration sample), and at 2 h, 4 h, 6 h, 9 h, 12 h, 18 h, 24 h, 36 h, and 48 h post‐dosing. Lutein concentration in plasma was determined using a novel, sensitive (theoretical limit of detection = 315 pg/ml; lower limit of quantitation = 2.5 ng/ml; upper limit of quantitation = 125 ng/ml), and precise [interday % coefficients of variation: 2.7% (2.5 ng/ml), 5.2% (12.5 ng/ml), 7.2% (125 ng/ml)] high performance liquid chromatographic method with ultraviolet‐visible detection, validated as specified by the European Agency for the Evaluation of Medicinal Products and the European Medicines Agency. Maximum plasma concentration (Cmax) and the area under the curve (AUC)0–48h were calculated for each animal in each period. Data were analyzed by analysis of variance followed Tukey's‐b post‐hoc test to determine differences in the Cmax and AUC0–48h among groups.ResultsFor both doses of each formulation, maximum plasma lutein concentrations occurred at 4–6 h and gradually returned to baseline by 24 h. For each dose, the Cmax (89, 112, 60, 79 ng/ml for 2.5 and 5 mg/kg Lutea, 2.5 and 5 mg/kg ELP, respectively) and the AUC0–48h (1390, 1874, 986, 1324 ng • h/ml for 2.5 and 5 mg/kg Lutea® 20, 2.5 and 5 mg/kg ELP, respectively) for lutein were approximately 40–50% greater in the Lutea® 20 formulation compared to the existing formulation (P < 0.05, Lutea® 20 vs ELP, for each parameter at each dose).ConclusionLutein (Lutea® 20), produced using a novel manufacturing technology, possesses superior oral bioavailability compared to an existing lutein‐containing product (ELP), and this observed superiority was likely due to the smaller crystal size of lutein in Lutea® 20 compared to lutein in ELP.Support or Funding InformationNovus International, St. Charles, MO USA