Determination of humanized anti-Tac in human serum by a sandwich enzyme linked immunosorbent assay

Fayer, B.E.; Soni, Peter; Binger, M.; Mould, Diane R.; Satoh, Hiroaki

doi:10.1016/0022-1759(95)00131-s

Cited by 20 publications

(6 citation statements)

References 17 publications

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“…The sensitivity limit for this assay was 0.1 μ g/mL for MPA and 2.38 μ g/mL for MPAG (in equivalent units to MPA) with an overall interassay coefficient of variation of 7.8% for MPA and 6.4% for MPAG. Daclizumab was measured in serum by a specific sandwich enzyme‐linked immunosorbent assay (ELISA) (9). The sensitivity limit for this assay was 25 ng/mL with an interassay coefficient of variation of 4–9%.…”

Section: Pharmacokinetic Variablesmentioning

confidence: 99%

Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation

Pescovitz

Bumgardner

Gaston

et al. 2003

Clinical Transplantation

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Daclizumab and mycophenolate mofetil (MMF) decrease the incidence of acute allograft rejection. This double-blind, randomized, placebo-controlled trial was performed primarily to assess the pharmacokinetics of MMF in an immunosuppressive regimen incorporating daclizumab. At five centers, 75 renal transplant recipients were randomized 2:1 to receive either daclizumab 1 mg/kg or placebo pre-transplantation and every other week, for a total of five doses. All patients received cyclosporine, steroids, and MMF. Levels of mycophenolic acid (MPA), its glucuronide metabolite, and daclizumab were measured after dosing on days 28 and 56. Safety parameters evaluated included: adverse events, laboratory abnormalities, infections, patient/graft survival, incidence of lymphoproliferative disorders, and incidence of acute rejection at 12 months. The concomitant administration of daclizumab and MMF had no effect on the pharmacokinetics of MPA: AUC(0-8) values (microg h/mL +/- SD) on day 28 were 30.1 +/- 13.3 for daclizumab-treat patients vs. 31.1 +/- 12.4 for placebo and on day 56, 37.7 +/- 18.2 for daclizumab-treated patients vs. 35.7 +/- 14.0 for placebo. Adverse events were similar between the two groups. Acute rejection at 12 months occurred in 14% of patients receiving daclizumab and 20% of patients receiving placebo. The coadministration of daclizumab did not result in a pharmacokinetic interaction with MPA, the active metabolite of MMF.

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Section: Pharmacokinetic Variablesmentioning

confidence: 99%

Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation

Pescovitz

Bumgardner

Gaston

et al. 2003

Clinical Transplantation

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“…Additional blood samples were collected prior to the second (day 14) and third (day 28) doses and on post‐transplantation days 59, 63, 70, and 84. Serum levels of daclizumab were measured by a specific sandwich ELISA using purified, soluble IL‐2Rα coated on microtiter plates as the capture reagent, with the serum competing with peroxidase‐labeled daclizumab incubated simultaneously (16). Samples were assayed for daclizumab concentration by Covance Laboratories Inc. (9200 Leesburg Pike; Vienna, VA, USA).…”

Section: Methodsmentioning

confidence: 99%

Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients

Pescovitz

Knechtle

Alexander

et al. 2007

Pediatric Transplantation

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This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6-12 yr (n = 18), and 13-17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 microg/mL (2.48-8.78), 4.54 microg/mL (1.79-18.7), and 4.94 microg/mL (0.05-10.6) in the less than or equal to five yr (n = 15), 6-12 yr (n = 17), and 13-17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg x h/mL (1585-3778), 2757 mg x h/mL (1873-3494) and 3297 mg x h/mL (1705-6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.

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“…In the ELISA design,13 microplates were coated with IL‐2Rα to capture daclizumab. A goat anti‐human F c γ fragment specific immunoglobulin G – HRP (horseradish perioxidase) conjugate was used for detection via optical absorption of 1,3,5‐trimethoxybenzene (TMB) in solution.…”

Section: Methodsmentioning

confidence: 99%

A novel three-dose regimen of daclizumab in liver transplant recipients with hepatitis C: A pharmacokinetic and pharmacodynamic study

et al. 2006

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This study evaluated the pharmacokinetics and pharmacodynamics of a novel 3-dose regimen of daclizumab in de novo hepatitis C liver transplant recipients. In 30 of 156 recipients receiving daclizumab, mycophenolate mofetil, tacrolimus, and no steroids (Arm 3 of Hep C 3 Liver Study), daclizumab (2, 2, and 1 mg/kg, respectively) was given on days 1, 3, and 8 posttransplant, respectively, with trough, peak (C max ), and CD25 saturation (CD sat ) measured sequentially. Mean daclizumab C max was 50.3 g/mL on day 1, and mean trough levels were 21.8, 25.7, and 9.9 g/mL on days 3, 8, and 30, respectively. A significant decline in CD sat (mean, 15.7% to 4.7%) was observed on day 1 and was sustained throughout the study (2.8% on day 30). Daclizumab concentration Ն5 g/mL was the level where most of the effect on CD sat was noticed. Elevated baseline CD sat was observed in African Americans, patients weighing Յ75 kg, and patients Ͻ60 years of age. After 365 days, 2 patients had experienced 3 rejections, 10 patients had recurrent hepatitis C, 4 patients died, and 2 grafts were lost. In conclusion, this novel 3-dose regimen is effective in rapidly achieving high therapeutic concentration of daclizumab and a significant decline in CD sat lasting over 30 days. Daclizumab (Zenapax, Roche Laboratories, Basel, Switzerland) is a highly specific humanized anti-interleukin 2 receptor (IL-2R) monoclonal antibody approved for induction therapy in renal transplant patients. Daclizumab specifically binds to the CD25 subunit of activated lymphocytes and specifically interferes with IL-2 signaling and receptors by inhibiting binding and phosphorylation of the IL-2R beta and gamma chains. Due to its high affinity for the CD25 subunit, daclizumab is an effective IL-2 inhibitor suppressing T-cell activity in the cellular immune response to allograft rejection.

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Determination of humanized anti-Tac in human serum by a sandwich enzyme linked immunosorbent assay

Cited by 20 publications

References 17 publications

Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation

Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation

Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients

A novel three-dose regimen of daclizumab in liver transplant recipients with hepatitis C: A pharmacokinetic and pharmacodynamic study

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