Population pharmacokinetics of carboplatin in children.
OBJECTIVE
In pediatric patients, administration of carboplatin according to body surface area results in a large variation in the area under the plasma ultrafilterable carboplatin concentration versus time curve. A population pharmacokinetic study using the NONMEM program was undertaken to determine the effects of a variety of covariates on the clearance of ultrafilterable carboplatin.


METHODS
Plasma carboplatin pharmacokinetics were determined in 57 children (2 months to 18 years old, with serum creatinine levels ranging from 27 to 268 mumol/L) treated for various tumor types.


RESULTS
The best fit corresponded to the formula: clearance (ml/min) = 2.85.weight.(1-0.00357.serum creatinine).(1-0.372.Np) + 8.7 (with serum creatinine in micromoles per liter, weight in kilograms, and Np = 1 or 0 for unilateral nephrectomy or not, respectively). The interindividual variability in clearance, as expressed by the coefficient of variation, decreased from 74% (no covariates) to 49% by taking account of weight, and to 29% under the final regression formula.


CONCLUSIONS
The ability of this formula to predict carboplatin clearance in children should be evaluated prospectively and compared to a method based on the determination of the glomerular filtration rate.
Chatelut
E
E
Centre Claudius Regaud, Toulouse, France.
Boddy
A V
AV
Peng
B
B
Rubie
H
H
Lavit
M
M
Dezeuze
A
A
Pearson
A D
AD
Roché
H
H
Robert
A
A
Newell
D R
DR
Canal
P
P
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001830:Body Surface Area; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D008297:Male; D015999:Multivariate Analysis; D009369:Neoplasms / Q000378:metabolism*; D012044:Regression Analysis
D000970:Antineoplastic Agents; D003404:Creatinine; D016190:Carboplatin