Pharmacokinetics of clofarabine in patients with high-risk inherited metabolic disorders undergoing brain-sparing hematopoietic cell transplantation

Janel Long-Boyle, Jiayin Huang, Nancy Rydholm, Angela Smith, Paul Orchard, Jakub Tolar, Pamala Jacobson

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Clofarabine, a newer purine analog with reduced central nervous system toxicity, may prove advantageous in hematopoietic cell transplantation in patients for whom neurotoxicity is a natural part of disease progression. This study evaluated clofarabine pharmacokinetics in adult and pediatric patients undergoing hematopoietic cell transplantation for the treatment of high-risk, inherited metabolic disorders. Clofarabine (40 mg/m2/d) was administered intravenously on days -7 to -3. Kinetic sampling occurred with doses 1 and 5, along with a single level collected on day of transplant (day0). Sixteen patients were studied with a median (range) age and body surface area (BSA) of 7.5 years (0.5-43) and 0.94 m2 (0.31-2.3), respectively. Clofarabine area under the concentration-time curve from time 0 to infinity was 931 ng•h/mL (685-1876), maximum concentration was 226 ng/mL (162-600), and minimum concentration was 3.2 ng/mL (1.7-5.6). Clofarabine clearance was 1.6 L/h/kg (0.7-2.4) and weakly correlated with weight (r 2 = 0.33) and BSA (r 2 = 0.26). No difference in plasma concentrations was found between dose 1 and dose 5 (all P >.05). All concentrations were below the limit of quantification (1 ng/mL) on day 0 in patients with normal renal function. Variability in clofarabine clearance was approximately 3-fold and was not adequately explained by covariates describing renal function and body size. In patients with adequate renal function, no drug accumulation occurs with consecutive daily dosing.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalJournal of Clinical Pharmacology
Volume51
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Clofarabine
  • hematopoietic cell transplantation
  • inherited metabolic disorders
  • pediatrics
  • pharmacokinetics

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