title: Cyclophosphamide and ifosfamide metabolites in the cerebrospinal fluid of children.
abstract: Although both cyclophosphamide (CP) and ifosfamide (IF) are used in the treatment of central nervous system tumors, little is known about the concentration of either drug or their metabolites in the cerebrospinal fluid (CSF) of children. The concentrations of the parent oxazaphosphorine and its principal metabolites were measured simultaneously in the plasma and CSF of 25 children. Twenty-one patients received CP for the treatment of either acute lymphoblastic leukemia, non-Hodgkin's lymphoma, or medulloblastoma, and 4 children received IF for the treatment of rhabdomyosarcoma. A high degree of interpatient variation was seen in terms of the CSF concentration of CP and the CSF:plasma ratio. The CSF:plasma ratio was greater for IF than for CP (P < 0.001). In contrast to IF, where the majority of metabolites was measured in the CSF, no child receiving CP had detectable metabolites. Children receiving dexamethasone had lower concentrations of CP in the CSF (P = 0.04). The CSF:plasma ratio for isophosphoramide mustard was greater than that for either parent drug or any other metabolite. These results demonstrate that IF enters the CSF to a greater extent than CP in children. The ability of both IF and CP and their metabolites to cross the blood-brain barrier may be reduced by dexamethasone.
authors.affiliation: Pharmacogenetics Research Unit, Department of Pharmacological Sciences, University of Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: S M
authors.initials: SM
authors.lastname: Yule
authors.forename: L
authors.initials: L
authors.lastname: Price
authors.forename: A D
authors.initials: AD
authors.lastname: Pearson
authors.forename: A V
authors.initials: AV
authors.lastname: Boddy
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001711:Biotransformation; D001932:Brain Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007223:Infant; D008228:Lymphoma, Non-Hodgkin / Q000134:cerebrospinal fluid / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D018242:Neuroectodermal Tumors, Primitive / Q000134:cerebrospinal fluid / Q000188:drug therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid / Q000188:drug therapy; D012208:Rhabdomyosarcoma / Q000134:cerebrospinal fluid / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D007069:Ifosfamide