title: Comparable efficacy with varying dosages of glucarpidase in pediatric oncology patients.
abstract: BACKGROUND
  Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate-induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced-dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients.
  
  
  METHODS
  The authors evaluated data from 26 patients who received glucarpidase after high-dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg.
  
  
  RESULTS
  No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P > 0.1) or HPLC (P > 0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98-100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2-100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P > 0.8).
  
  
  CONCLUSIONS
  The efficacy of glucarpidase in the treatment of HDMTX-induced kidney injury was not dosage-dependent in this retrospective analysis of pediatric oncology patients.
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Jeffrey R
authors: JR
authors: Scott
authors: Biostatistics Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Yinmei
authors: Y
authors: Zhou
authors: Biostatistics Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Cheng
authors: C
authors: Cheng
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Deborah A
authors: DA
authors: Ward
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Hope D
authors: HD
authors: Swanson
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Alejandro R
authors: AR
authors: Molinelli
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Clinton F
authors: CF
authors: Stewart
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.|Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
authors: Fariba
authors: F
authors: Navid
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Sima
authors: S
authors: Jeha
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Mary V
authors: MV
authors: Relling
authors: Pharmaceutical Department, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors: Kristine R
authors: KR
authors: Crews
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016527:Drug Costs; D004341:Drug Evaluation; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D012516:Osteosarcoma / Q000097:blood / Q000150:complications / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D020127:Recovery of Function; D012189:Retrospective Studies; D055815:Young Adult; D011623:gamma-Glutamyl Hydrolase / Q000008:administration & dosage* / Q000191:economics / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D011994:Recombinant Proteins; D003404:Creatinine; D011623:gamma-Glutamyl Hydrolase; D002955:Leucovorin; D008727:Methotrexate
keywords: carboxypeptidase; glucarpidase; methotrexate; nephrotoxicity; pediatric
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