Pharmacokinetics of high-dose melphalan in children and adults

Melphalan pharmacokinetics were studied in 20 children with stage IV neuroblastomas or Ewing's sarcomas and in 10 adults with AML, ALL, or small cell lung carcinomas, after IV administration of high doses (140 mg/m2 with furosemide-induced diuresis and 180 mg/m2 without induced diuresis) and high fluid intake (3000 ml/m2/day). Unchanged melphalan was assayed in plasma and cerebrospinal fluid by means of a high-performance liquid chromatographic procedure. The elimination half-life (t1/2 less than 80 min) allows autologous bone marrow transplantation 24 h after the drug administration. In some children we were able to detect melphalan in cerebrospinal fluid samples.