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

Background: Basiliximab is a high-affinity interleukin-2 receptor (CD25) ch imeric monoclonal antibody used for immunoprophylaxis in organ transplantat ion. It was assessed in a randomized, double-blind, placebo-controlled effi cacy trial in de novo liver allograft recipients who received 40 mg of basi liximab (20 mg on days 0 and 4) in addition to baseline immunosuppression w ith cyclosporine (INN, ciclosporin) microemulsion and corticosteroids. Methods: Serial blood samples (8.3 +/- 1.4 per patient) were collected duri ng 12 weeks after transplantation from 184 basiliximab-treated patients, an d empirical Bayes estimates of each patient's disposition parameters were d erived. Demographic-clinical covariates were explored with regression metho ds. 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 ba siliximab disposition; however, the cumulative volume of drained ascites fl uid in the first week was positively correlated with clearance. Receptor-sa turating basiliximab concentrations (greater than or equal to0.1 mug/mL) we re maintained for 38 +/- 16 days, and this was negatively correlated with t he cumulative volume of drained ascites fluid in week 1. Patients who exper ienced an acute rejection episode did not clear basiliximab at a faster rat e than their rejection-free peers nor did they maintain CD25-saturating con centrations 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 majori ty of patients with liver transplants, a supplemental dose at the end of th e first week may be considered for those with substantial (>10 L) postopera tive ascites fluid drainage.