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A population pharmacokinetic screen to identify demographic‐clinical covariates of basiliximab in liver transplantation
Author(s) -
Kovarik John M.,
Nashan Björn,
Neuhaus Peter,
Clavien PierreAlain,
Gerbeau Christophe,
Hall Michael L.,
Korn Alexander
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2001.114887
Subject(s) - basiliximab , medicine , transplantation , population , liver transplantation , gastroenterology , volume of distribution , ciclosporin , pharmacokinetics , urology , surgery , kidney transplantation , environmental health
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 (≥0.1 μg/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. Clinical Pharmacology & Therapeutics (2001) 69 , 201–209; doi: 10.1067/mcp.2001.114887