title: A novel three-dose regimen of daclizumab in liver transplant recipients with hepatitis C: a pharmacokinetic and pharmacodynamic study.
abstract: 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 microg/mL on day 1, and mean trough levels were 21.8, 25.7, and 9.9 microg/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 > or = 5 microg/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 < or = 75 kg, and patients <60 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.
authors.affiliation: Transplant Center, University of Texas Health Science Center at San Antonio, TX 78229-3900, USA. washburn@uthscsa.edu
authors.forename: W Kenneth
authors.initials: WK
authors.lastname: Washburn
authors.forename: Lewis W
authors.initials: LW
authors.lastname: Teperman
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Heffron
authors.forename: David D
authors.initials: DD
authors.lastname: Douglas
authors.forename: Steven
authors.initials: S
authors.lastname: Gay
authors.forename: Eliezer
authors.initials: E
authors.lastname: Katz
authors.forename: Goran B G
authors.initials: GB
authors.lastname: Klintmalm
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006439:Hemodynamics / Q000187:drug effects*; D006526:Hepatitis C / Q000601:surgery*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012449:Safety; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab