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

✍ Scribed by W. Kenneth Washburn; Lewis W. Teperman; Thomas G. Heffron; David D. Douglas; Steven Gay; Eliezer Katz; Goran B.G. Klintmalm

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 161 KB
• Volume: 12
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.20631

✦ Synopsis

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.