title: Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporine and steroids in renal transplantation.
abstract: 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.
authors.affiliation: Indiana University, Indianapolis, IN 46202, USA. mpescov@iupui.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: Ginny
authors.initials: G
authors.lastname: Bumgardner
authors.forename: Robert S
authors.initials: RS
authors.lastname: Gaston
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kirkman
authors.forename: Susan
authors.initials: S
authors.lastname: Light
authors.forename: Indravadan H
authors.initials: IH
authors.lastname: Patel
authors.forename: Keith
authors.initials: K
authors.lastname: Nieforth
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
mesh_terms: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000627:therapeutic use*; D000077561:Daclizumab; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D005965:Glucuronates / Q000097:blood; D020719:Glucuronides; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D016030:Kidney Transplantation; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D005965:Glucuronates; D020719:Glucuronides; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C113145:mycophenolic acid glucuronide; D016572:Cyclosporine; D000077561:Daclizumab; D009173:Mycophenolic Acid; D011241:Prednisone; D008775:Methylprednisolone