Pharmacokinetics and acute renal effects of continuously infused carboplatin.
Carboplatin was given as a 24-hour infusion at high doses to pediatric patients with cancer (n = 11) and pharmacokinetic parameters and renal effects were determined. Median carboplatin clearance for course 1 (151 ml/min per 1.73 m2;) was not significantly different from clearance for course 2 (144 ml/min per 1.73 m2; p = 0.33). The median glomerular filtration rate measured before (159 ml/min per 1.73 m2) and after course 1 (161 ml/min per 1.73 m2) did not differ significantly (p = 0.4). Binding was time dependent but modest with a median free fraction at the end of infusion of 0.82. Pharmacokinetic parameters for continuous-infusion carboplatin are similar to those reported for short infusions, but the median dose of 817 mg/m2 required to achieve an acceptable systemic exposure in these patients was 45% greater than the previously suggested maximum tolerated dosage. Continuous infusion carboplatin did not alter carboplatin clearance or adversely effect glomerular filtration rate during a second course, showing the feasibility of this alternative dosage strategy to enhance therapeutic effects.
Murry
D J
DJ
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105.
Sandlund
J T
JT
Stricklin
L M
LM
Rodman
J H
JH
D000293:Adolescent; D002051:Burkitt Lymphoma / Q000188:drug therapy; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D016018:Least-Squares Analysis; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy
D016190:Carboplatin