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.
OBJECTIVE
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 microg/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-gamma (IFN-gamma) concentration was 24-72 h. However, in monkeys receiving continuous dosing of rhIL-12, serum IFN-gamma concentration was very low or even undetectable.


CONCLUSIONS
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.
Department of Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Rubing
R
Li
Fengjun
F
Deng
Yonghang
Y
Fu
Yijun
Y
Zhang
Huayin
H
Wan
Dan
D
Zhou
Jingliang
J
Gu
Jiangping
J
Xu
D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008252:Macaca fascicularis; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12