Nonclinical pharmacokinetics of E3112, a recombinant human hepatocyte growth factor, in rats and monkeys by a simple ELISA kit assay

• Published in: Journal of pharmacological and toxicological methods 2024-07, Vol.128, p.107541, Article 107541
• Main Authors: Aoyama, Muneo, Mano, Yuji
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Animals; Dose-Response Relationship, Drug; E3112; ELISA; Enzyme-Linked Immunosorbent Assay - methods; Female; Hepatocyte growth factor; Hepatocyte Growth Factor - blood; Hepatocyte Growth Factor - pharmacokinetics; Humans; Injections, Intravenous; Macaca fascicularis; Male; Monkeys; Pharmacokinetics; Rats; Rats, Sprague-Dawley; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacokinetics; Reproducibility of Results
• ISSN: 1056-8719; 1873-488X; 1873-488X
• DOI: 10.1016/j.vascn.2024.107541

E3112 is a recombinant human hepatocyte growth factor which is under development for the treatment of acute liver failure. Pharmacokinetics (PK) evaluation in experimental animals is important and thus a simple assay for the determination of E3112 in rat and monkey serum has been validated using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. E3112 in rat and monkey serum was quantifiable from 0.313 ng/mL to 15.0 ng/mL without prozone effects. Dilution integrity enabled accurate assay up to 500,000-fold dilution. Accuracy and precision were within the acceptance criteria. PK of E3112 was investigated after intravenous administration to rats and monkeys. PK of E3112 was similar between male and female animals in both species. Nonlinear PK of E3112 was observed in rats after intravenous bolus dose at 1–100 mg/kg while nonlinear PK was not significant in monkeys after intravenous infusion at 0.5–25 mg/kg. These findings suggest that the assay of E3112 in serum using a commercially available ELISA kit was validated and successfully applied to PK studies in rats and monkeys.