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 (TM) (rabbit anti-thymocyte globulin), 1.5 mg/kg/day for 6-14 days as part of a double-blinded trial comparing the ef ficacy of Thymoglobulin and Atgam (TM) (horse anti-thymocyte globulin). Ser ial serum samples from the patients were tested to determine the level of T hymoglobulin (i.e. rabbit IgG levels = total Thymoglobulin) and anti-Thymog lobulin using ELISAs. Antibodies binding to human lymphocytes (active Thymo globulin), were determined by flow cytometry; no correlation was seen betwe en treatment efficacy and either active or total Thymoglobulin concentratio ns; the overall treatment success rate was 86%. Pharmacokinetics of total a nd active Thymoglobulin were distinctly different; active Thymoglobulin dis appeared much more rapidly: only 12% of patients had detectable active Thym oglobulin by day 90 compared to 81% of patients with detectable total Thymo globulin; percent active Thymoglobulin decreased from a peak of 0.56-0.7% d uring treatment, to 0.07-0.35% by day 21, and less than 0.14% by day 30. Th ymoglobulin and active Thymoglobulin concentrations were modeled by multipl e 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 t hat: (1) for a group of patients receiving primary Thymoglobulin treatment (averaging nine full and one partial dose per patient), neither Thymoglobul in nor active Thymoglobulin levels are predictive of treatment outcome; (2) active Thymoglobulin disappears more rapidly from the circulation than tot al Thymoglobulin; and (3) patients that develop anti-rabbit IgG antibodies clear Thymoglobulin and active Thymoglobulin more rapidly than unsensitized patients. (C) 2001 Elsevier Science B.V. All rights reserved.