High dose melphalan in children with advanced malignant disease. A pharmacokinetic study.
Nine children with poor-prognosis malignancies--seven with advanced neuroblastoma and two with metastatic Ewing's sarcoma--were given high doses of melphalan (HDM), 150 mg/m2 (3 patients) and 180 mg/m2 (6 patients), as a 'late intensification' agent combined with noncryopreserved autologous bone marrow transplants. Melphalan levels in the plasma decreased biphasically, with mean half-lives of 6.6 min and 3.0 h. At the time of marrow reinfusion (12-21 h after HDM) the melphalan plasma level was generally below 0.1 microgram/ml. The renal contribution to melphalan clearance was low, a mean of 5.8% of the injected dose being found in patients' urine over the 12 h following HDM administration. No significant difference was seen in pharmacokinetic parameters between patients undergoing and not undergoing forced diuresis.
D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000378:metabolism
D008558:Melphalan