A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations.
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.
Kovarik
John M
JM
Novartis Pharmaceuticals, Basel, Switzerland.
Offner
Gisela
G
Broyer
Michel
M
Niaudet
Patrick
P
Loirat
Chantal
C
Mentser
Mark
M
Lemire
Jacques
J
Crocker
John F
JF
Cochat
Pierre
P
Clark
Godfrey
G
Gerbeau
Christophe
C
Chodoff
Lawrence
L
Korn
Alexander
A
Hall
Michael
M
D000465:Algorithms; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077552:Basiliximab; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000097:blood; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007275:Injections, Intravenous; D016030:Kidney Transplantation; D008297:Male; D011182:Postoperative Care; D011300:Preoperative Care; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000097:blood; D011993:Recombinant Fusion Proteins; D014184:Transplantation, Homologous
D000906:Antibodies; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab