TY - JOUR
T1 - Pharmacokinetics of clofarabine in patients with high-risk inherited metabolic disorders undergoing brain-sparing hematopoietic cell transplantation
AU - Long-Boyle, Janel
AU - Huang, Jiayin
AU - Rydholm, Nancy
AU - Smith, Angela
AU - Orchard, Paul
AU - Tolar, Jakub
AU - Jacobson, Pamala
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Clofarabine
KW - hematopoietic cell transplantation
KW - inherited metabolic disorders
KW - pediatrics
KW - pharmacokinetics
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U2 - 10.1177/0091270010372519
DO - 10.1177/0091270010372519
M3 - Article
C2 - 20525919
AN - SCOPUS:79955549083
SN - 0091-2700
VL - 51
SP - 679
EP - 686
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 5
ER -