Population Pharmacokinetics and Exposure-Response Relationships for Basiliximab in Kidney Transplantation

Abstract

There were no demographic or clinical subpopulations not adequately treated with the standard basiliximab dosing regimen. Over the range of CD25 suppression durations observed in this study, extended periods of receptor blockade did not seem to confer an immunoprophylactic advantage compared with shorter periods of receptor suppression.

A Multicenter, Prospective, Randomized, Double-Blind Trial of Basiliximab in Heart Transplantation

“…14,26 Both the basiliximab pharmacokinetic data reported here for heart transplant recipients and the duration of CD25-saturating serum concentrations were in the ranges cited in kidney transplantation. 12 There was no indication that patients with AR episodes were underexposed to basiliximab or immunosuppressed for a shorter period of time compared with their rejectionfree peers in this study. As in kidney and liver transplantation, the incidence of immunogenicity from basiliximab was low with respect to anti-idiotype antibodies in heart transplantation.…”

“…Concentration-time data were evaluated with a non-linear mixed-effects pharmacostatistical model to derive basic pharmacokinetic parameters. 12 The duration that serum basiliximab concentrations exceeded the saturation threshold of 0.2 g/ml was determined for each patient based on the measured concentrations and the patient's elimination half-life. This was used as an estimate of the duration of CD25-receptor saturation.…”

Lower Risk of Infectious Deaths in Cardiac Transplant Patients Receiving Basiliximab Versus Anti-thymocyte Globulin as Induction Therapy

“…Approximately one third of first rejection episodes in the basiliximab cohort occurred at 2 to 3 months post-transplant. CD25 inhibition is maximal with basiliximab induction for between 30 and 45 days, 19 which underscores the need to ensure adequate maintenance immunosuppression during the time when the effect of IL-2RA induction is declining.…”

Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy

“…Once given the antibodies remain in the circulation for several weeks, the duration depending on the other immunosuppressive therapy being taken. With prednisolone and cyclosporine, receptor saturating concentrations remain for around 7 weeks [192]; the addition of azathioprine or MMF extends the duration of action (50 and 59 days, respectively) [193]. Anti-CD25 mAbs do not trigger a strong antiglobulin (HAMA) response, although occasional anaphylactic reactions to re-challenge with the antibody are described [194].…”