Pharmacokinetics and Pharmacodynamics of Anthocyanins after Administration of Tart Cherry Juice to Individuals with Gout

Scope Tart cherries (TCs) contain high levels of anthocyanins that exert potent antioxidant and antiinflammatory effects and potentially benefit individuals with gout. Methods and results This study aims to quantitate the major anthocyanins in TC Juice Concentrate (TCJC) and identify the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of the major anthocyanin cyanidin‐3‐glucosylrutinoside (C3GR). A PK‐PD study enrolling human subjects with a history of gout is performed. Subjects are randomized to receive either 60 or 120 mL of TCJC. Anthocyanins are quantitated using liquid chromatography‐mass spectroscopy (LCMS). Antioxidant and antiinflammatory mRNA expression is measured using real‐time qPCR before and after the administration of TCJC. A population PK model (popPK) is fit to the experimental data, and an indirect PD model (IDR) is constructed in Monolix. Conclusion Of the bioavailable anthocyanins, C3GR achieves the highest plasma concentration in a dose‐dependent manner. A popPK predicts anthocyanin exposure, and an IDR produces reasonable approximations of PD effects. Individuals with gout receive 60 or 120 mL of tart cherry juice concentrate (TCJC). Blood is collected, and the plasma component is used to quantitate major anthocyanins; leukocytes to assess changes in gene expression. Subjects provide a stool sample which is used to perform ex vivo culture studies. Pharmacokinetic and pharmacodynamic modeling is performed.