Total and active thymoglobulin levels: effects of dose and sensitization on serum concentrations.
A group of 79 renal transplant patients undergoing acute rejection episodes were treated with Thymoglobulin (rabbit anti-thymocyte globulin), 1.5 mg/kg/day for 6-14 days as part of a double-blinded trial comparing the efficacy of Thymoglobulin and Atgam (horse anti-thymocyte globulin). Serial serum samples from the patients were tested to determine the level of Thymoglobulin (i.e. rabbit IgG levels = total Thymoglobulin) and anti-Thymoglobulin using ELISAs. Antibodies binding to human lymphocytes (active Thymoglobulin), were determined by flow cytometry; no correlation was seen between treatment efficacy and either active or total Thymoglobulin concentrations; the overall treatment success rate was 86%. Pharmacokinetics of total and active Thymoglobulin were distinctly different; active Thymoglobulin disappeared much more rapidly: only 12% of patients had detectable active Thymoglobulin by day 90 compared to 81% of patients with detectable total Thymoglobulin; percent active Thymoglobulin decreased from a peak of 0.56-0.7% during treatment, to 0.07-0.35% by day 21, and less than 0.14% by day 30. Thymoglobulin and active Thymoglobulin concentrations were modeled by multiple regression. Using dose number and sensitization as independent variables, 47-76% of the variability seen in interpatient Thymoglobulin levels could be explained, while for active Thymoglobulin levels, the measured variables accounted for 13-48% of the observed interpatient variation. We conclude that: (1) for a group of patients receiving primary Thymoglobulin treatment (averaging nine full and one partial dose per patient), neither Thymoglobulin nor active Thymoglobulin levels are predictive of treatment outcome; (2) active Thymoglobulin disappears more rapidly from the circulation than total Thymoglobulin; and (3) patients that develop anti-rabbit IgG antibodies clear Thymoglobulin and active Thymoglobulin more rapidly than unsensitized patients.
Regan
J F
JF
SangStat Medical Corporation, Fremont, CA 94555, USA.
Lyonnais
C
C
Campbell
K
K
Smith
L V
LV
Buelow
R
R
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006084:Graft Rejection / Q000628:therapy*; D006207:Half-Life; D006736:Horses; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D010599:Pharmacokinetics; D011817:Rabbits; D013045:Species Specificity; D013601:T-Lymphocytes; D014184:Transplantation, Homologous / Q000276:immunology; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D007074:Immunoglobulin G