The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man.
The pharmacokinetics of the distribution and elimination of polyclonal rabbit antithymocyte globulin (ATG) following intravenous infusion was studied in patients who had received renal allografts. ATG concentration was measured using a new enzyme-linked immunoabsorbent assay (ELISA) for the Fc portion of rabbit IgG. Eleven patients received 14 courses of ATG supplied either by Fresenius (F-ATG) or Merieux (M-ATG) as a daily infusion of 2-6 mg/kg body weight for a therapeutic course lasting 5-10 days. The washout phase of ATG elimination was analysed over 0-300 days; results were well-fitted by a single exponential decay (r2 > 0.95) giving a mean elimination half-life (t0.5e) of 29.8 days (range 14.3-45.0, n = 9). Data for the first 4 days of treatment were analysed with linear regression to obtain a mean value for the apparent volume of distribution of ATG (Vd) of 0.12 l/kg body weight (range 0.07 to 0.17, n = 5). These results demonstrate that rabbit ATG has a long half-life in human plasma and an apparent volume of distribution of about twice plasma volume. The relationship between the concentration of ATG measured by this Fc receptor assay and its biological activity requires further study.
Bunn
D
D
Renal Unit, King's College Hospital (Dulwich), London, UK.
Lea
C K
CK
Bevan
D J
DJ
Higgins
R M
RM
Hendry
B M
BM
D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000378:metabolism*; D001379:Azathioprine / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006084:Graft Rejection / Q000517:prevention & control*; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D016030:Kidney Transplantation; D016014:Linear Models; D011239:Prednisolone / Q000008:administration & dosage; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine