Toxicokinetics of recombinant human fibroblast growth factor 21 for injection in cynomolgus monkey for three months

Recombinant human fibroblast growth factor 21 (FGF-21) is a potential therapeutic agent for multiple metabolic diseases. However, little is known about the toxicokinetic characteristics of FGF-21. In the present study, we investigated the toxicokinetics of FGF-21 delivered via subcutaneous injection in vivo . Twenty cynomolgus monkeys were injected subcutaneously with different doses of FGF-21 for 86 days. Serum samples were collected at eight different time points (0, 0.5, 1.5, 3, 5, 8, 12, and 24 h) on day 1 (d1), d37, and d86 for toxicokinetic analysis. The serum concentrations of FGF-21 were measured using a double sandwich ELISA. Necropsy and pathological analysis were performed on d87 and d116 (after recovery for 29 days). The average AUC (0-24h) values of low-dose FGF-21 on d1, d37, and d86 were 5253, 25268, and 60445 μg·h/L, and the average AUC (0-24h) values of high-dose FGF-21 on d1, d37, and d86 were 19964, 78999, and 1952821 μg·h/L, respectively. The peak concentrations ( C max ) of low-dose FGF-21 on d1, d37, and d86 were 621.1, 2767.9, and 4182.0 μg/L, respectively. The C max values of high-dose FGF-21 on d1, d37, and d86 were 2196.8, 6637.5, and 13430.4 μg/L, respectively. The elimination half-lives ( t 1/2z ) of low- and high-dose FGF-21 on d1, d37, and d86 were 3.1–4.8, 4.2–6.7, and 6.2–8.8 h, respectively. The anatomical and pathological results showed that continuous subcutaneous injection of FGF-21 for 86 days did not affect organ weight, the organ coefficient, and histopathology in cynomolgus monkeys. Our results have guiding significance for the preclinical research and clinical use of FGF-21.