Pharmacokinetics of 2-chlorodeoxyadenosine in a child undergoing hemofiltration and hemodialysis for acute renal failure.
The clearance of 2-chlorodeoxyadenosine (2-CdA) in patients with renal insufficiency has not been characterized previously. The authors describe the clinical course and the pharmacokinetics of 2-CdA in a child with acute monoblastic leukemia who experienced acute renal failure during treatment with cytarabine and 2-CdA. 2-CdA (9 mg/m per day) was infused over 30 minutes daily for 5 days. Plasma and dialysate concentrations of 2-CdA were measured by high-performance liquid chromatography. The rate of this patient's 2-CdA clearance was lower than the rates reported for children with normal renal function. The average clearance rate, reflecting systemic clearance and clearance by continuous venovenous hemofiltration and hemodialysis, was 12.4 L/hour per m for the first 3 days of 2-CdA therapy. He did not experience untoward hematologic toxicity. Because high 2-CdA plasma concentrations were observed in this patient, clinicians are advised to exercise caution when using this drug in patients with renal dysfunction. More experience in the administration of 2-CdA to patients with renal insufficiency will be necessary to determine the need for dosage adjustment.
Crews
Kristine R
KR
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA. kristine.krews@stjude.org
Wimmer
Peggy S
PS
Hudson
Joanna Q
JQ
Howard
Scott C
SC
Ribeiro
Raul C
RC
Razzouk
Bassem I
BI
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001228:Aspergillosis / Q000150:complications; D002648:Child; D017338:Cladribine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D017809:Fatal Outcome; D006440:Hemofiltration; D006801:Humans; D007937:Leukapheresis; D007948:Leukemia, Monocytic, Acute / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D006435:Renal Dialysis; D014503:Urate Oxidase / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D011994:Recombinant Proteins; D003561:Cytarabine; D017338:Cladribine; D005047:Etoposide; D014503:Urate Oxidase; D003630:Daunorubicin