Pharmacokinetics,tissue distribution,and excretion of FGF‐21 following subcutaneous administration in rats

As one of the fibroblast growth factor (FGF) superfamily, FGF‐21 has been extensively investigated for its functions and roles since its discovery. It has been demonstrated to be one of the key regulators for glucose and lipid metabolism, and exhibits beneficial effects on cardiovascular disease. However, studies focusing on its pharmacokinetic behavior in vivo as a novel therapeutic agent have not been reported. In the present study, rapid and sensitive analytical approaches including radioactivity assay and assay after precipitation/separation by high performance liquid chromatography (HPLC) were established to determine the content of FGF‐21 tagged with ¹²⁵I in plasma, tissue, and excrement. The results indicated that FGF‐21 were quickly absorbed into systematic circulation and slowly eliminated; C_max and exposure increased in a dose‐dependent manner, exhibiting a typical linear pharmacokinetic pattern. Tissue distribution also confirmed that the kidney is the primary organ for FGF‐21 to be distributed, even though radioactivity of FGF‐21 was recovered in all tissues examined. In addition, the results also supported that urinary excretion was the critical route for FGF‐21 to be eliminated. The study fully clarifies the pharmacokinetic behavior of FGF‐21 and can provide valuable information and support further safety and toxicology development.