Plasma concentration of hGH and anti-hGH antibodies after subcutaneous administration of hGH for 3 weeks to immunosuppressed pigs

Objective: The objective of the present study was to evaluate the. dosing r egimen of immunosuppressants necessary to avoid the formation of anti-hGH a ntibodies in a pig model. Animals: Sixteen pigs were divided into four groups, Procedure: Three different immunosuppressive treatments were tested (group 1: Control (no treatment); group 2. 10 mg; group 3: 20 mg; and group 4: 40 mg cyclosporine; combined with 2 mg azatioprine and 2 mg prednisolone p.o./ kg/day). The treatments were given from days -7 to 22. All groups were dosed subcutaneously (s.c.) with 0.5 mg hGH/kg once daily f rom days 1 to 22. On the first and the last days of dosing blood samples we re collected to describe the hGH concentration versus time profile. Before dosing and on days 5, 10, and 15 blood samples were collected for measuring hGH antibody formation. Results: A dose-dependent decrease in white blood cell counts was observed in all immunosuppressive-treated groups. Groups 1 and 2 produced antibodies against hGH during the 22 days of dosing while the formation of antibodies was suppressed in groups 3 and 4. In the control group and group 2 the pha rmacokinetic parameters of hGH were influenced by the formation of anti-hGH antibodies. In groups 3 and 4, the pharmacokinetic parameters were compara ble on the first and the last day of dosing. Conclusion: The formation of anti-hGH antibodies influenced the pharmacokin etics of hGH in pigs, but it could be prevented by immunosuppressive therap y. From the present experiment, a dose of 20 mg cyclosporine, 2 mg azatiopr ine, and 2 mg prednisolone p.o./kg/day was able to prevent the pigs from pr oducing antibodies without having severe adverse effects. This model may by useful in future experiments using sustained release formulations of hGH, and possibly for other compounds that may induce antibody production in pig s. (C) 1999 Elsevier Science Inc.