Pharmacokinetics and acute renal effects of continuously infused carboplatin

Clin Pharmacol Ther. 1993 Oct;54(4):374-80. doi: 10.1038/clpt.1993.163.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Burkitt Lymphoma / drug therapy
  • Carboplatin / administration & dosage
  • Carboplatin / pharmacokinetics*
  • Carboplatin / pharmacology*
  • Child
  • Child, Preschool
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Infusions, Intravenous
  • Least-Squares Analysis
  • Lymphoma, Large B-Cell, Diffuse / drug therapy

Substances

  • Carboplatin