A population pharmacokinetic screen to identify demographic-clinical covariates of basiliximab in liver transplantation

被引:36
作者
Kovarik, JM
Nashan, B
Neuhaus, P
Clavien, PA
Gerbeau, C
Hall, ML
Korn, A
机构
[1] Novartis Pharmaceut, E Hanover, NJ USA
[2] Med Hsch Hannover, Hannover, Germany
[3] Free Univ Berlin, Klinikum Rudolf Virchow, D-1000 Berlin, Germany
[4] Duke Univ, Med Ctr, Durham, NC USA
关键词
D O I
10.1067/mcp.2001.114887
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids. Methods: Serial blood samples (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation from 184 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. Demographic-clinical covariates were explored with regression methods. Results: Basiliximab clearance was 55 +/- 26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/- 6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C seropositivity; and notable postoperative bleeding had no clinically relevant influences on basiliximab disposition; however, the cumulative volume of drained ascites fluid in the first week was positively correlated with clearance. Receptor-saturating basiliximab concentrations (greater than or equal to0.1 mug/mL) were maintained for 38 +/- 16 days, and this was negatively correlated with the cumulative volume of drained ascites fluid in week 1. Patients who experienced an acute rejection episode did not clear basiliximab at a faster rate than their rejection-free peers nor did they maintain CD25-saturating concentrations for a shorter period. Conclusions: Although the standard dose regimen of 20 mg of basiliximab on days 0 and 4 after transplantation appears to be appropriate for the majority of patients with liver transplants, a supplemental dose at the end of the first week may be considered for those with substantial (>10 L) postoperative ascites fluid drainage.
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页码:201 / 209
页数:9
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