Pharmacokinetics and Pharmacodynamics of Subcutaneous Injection and Intravenous Infusion of Recombinant Human Interleukin-12 and Recombinant Human Interleukin-12 Combined with Hepatitis B Surface Antigen in Cynomolgus Monkeys

Background/Aims: Interleukin-12 (IL-12) is a cytokine that plays an important role in cell-mediated immunity and shows great potential as a therapeutic agent for the treatment of tumors and infectious diseases. Methods: We investigated the pharmacokinetics (PK) and pharmacodynamics of recombinant human IL-12 (rhIL-12) and rhIL-12 combined with hepatitis B surface antigen (HB s Ag) after administration by subcutaneous (s.c.) injection or intravenous infusion in cynomolgus monkeys. Results: After s.c. injection of rhIL-12 at doses of 0.15–1.5 µg/kg, the monkey’s metabolism showed linear kinetic characteristics. The intramuscular injection of HB s Ag vaccine did not affect the pharmacokinetic profile of rhIL-12. In monkeys administered rhIL-12 in a continuous dosing fashion, serum rhIL-12 was undetectable, probably due to the neutralizing effect of anti-rhIL-12 antibodies. In monkeys receiving high-dose s.c. injection of rhIL-12, the T max for serum rhIL-12 concentration was 4–8 h, and the T max for serum interferon-γ (IFN-γ) concentration was 24–72 h. However, in monkeys receiving continuous dosing of rhIL-12, serum IFN-γ concentration was very low or even undetectable. Conclusion: We found that the PK of rhIL-12 was dose-dependent and its pharmacological effects appeared after T max and lasted much longer than mean retention time.