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PubMed · 12394838

A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations.

John M Kovarik·Gisela Offner·Michel Broyer·Patrick Niaudet·Chantal Loirat·Mark Mentser·Jacques Lemire·John F Crocker·Pierre Cochat·Godfrey Clark·Christophe Gerbeau·Lawrence Chodoff·Alexander Korn·Michael Hall
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Abstract

BACKGROUND: The pharmacokinetics and immunodynamics of basiliximab were assessed in 39 pediatric de novo kidney allograft recipients to rationally chose a dose regimen for this age group. METHODS: In study part 1, patients were given 12 mg/m(2) of basiliximab by bolus intravenous injection before surgery and on day 4. An interim pharmacokinetic evaluation supported a fixed-dose approach for study part 2 in which infants and children received two 10-mg doses and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for analysis of basiliximab and soluble interleukin-2 receptor concentrations, flow cytometry, and screening for anti-idiotype antibodies. RESULTS: Basiliximab clearance in infants and children (n=25) was reduced by approximately half compared with adults from a previous study and was independent of age (1-11 years), weight (9-37 kg), and body surface area (0.44-1.20 m(2) ). Clearance in adolescents (12-16 years, n=14) approached or reached adult values. CD25-saturating basiliximab concentrations were maintained for 31+/-12 days in study part 1 with mg/m(2) dosing and for 36+/-14 days in study part 2 based on the fixed-dose regimen ( P=0.31). A single patient experienced a rejection episode during CD25 saturation. The duration of CD25 saturation in patients who experienced a rejection episode after desaturation did not differ from those who remained rejection-free for the full 6-month period: 34+/-6 days (n=6) vs. 35+/-14 days (n=33 patients); P=0.74. Anti-idiotype antibodies were detected in two patients; however, this did not influence the clearance of basiliximab or the duration of CD25 saturation. CONCLUSIONS: To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients <35 kg should receive two 10-mg doses and those > or =35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose is given before surgery and the second on day 4 after transplantation.

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AlgorithmsAntibodiesAntibodies, MonoclonalBasiliximabChildChild, PreschoolDose-Response Relationship, DrugDrug Administration ScheduleFemaleGraft RejectionHumansImmunoglobulin IdiotypesImmunosuppressive AgentsInjections, IntravenousKidney TransplantationMalePostoperative CarePreoperative CareProspective StudiesReceptors, Interleukin-2Recombinant Fusion ProteinsTransplantation, HomologousClinical TrialJournal ArticleMulticenter Study

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John M Kovarik, Gisela Offner, Michel Broyer, Patrick Niaudet, Chantal Loirat, Mark Mentser, Jacques Lemire, John F Crocker, Pierre Cochat, Godfrey Clark, Christophe Gerbeau, Lawrence Chodoff, Alexander Korn, Michael Hall. 2002-10-15. A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations.. https://doi.org/10.1097/00007890-200210150-00011

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