Abstract:
STUDY OBJECTIVES:To determine whether glomerular filtration rate (GFR) changes during induction chemotherapy in children with leukemia, and to examine GFR as a determinant of pharmacokinetic variability of methotrexate clearance. DESIGN:Prospective, unblinded observational study in consecutive patients. SETTING:A research hospital. PATIENTS:Thirty-eight children newly diagnosed with acute lymphoblastic leukemia. INTERVENTIONS:The patients received either high-dose methotrexate 1 g/m2 intravenously over 24 hours or low-dose methotrexate 30 mg/m2 orally every 6 hours for six doses; both regimens were followed by an intensive six-drug chemotherapy regimen given over 6 weeks. Glomerular filtration rate was determined in each subject before and at the conclusion of induction therapy. MEASUREMENTS AND MAIN RESULTS:The GFR was determined from 99mTc-DTPA serum clearance in all patients, and methotrexate clearance was estimated from serial serum concentrations in 18 of these children who received high-dose methotrexate. Median values for GFR at diagnosis (131 ml/min/1.73 m2) and after induction therapy (120 ml/min/1.73 m2) were not significantly different (p = 0.26) but were highly variable (range 49-274 ml/min/1.73 m2). Body size, age, and serum creatinine were correlated significantly with GFR at diagnosis. Amphotericin B therapy (6 patients) significantly decreased GFR (p = 0.046) without a corresponding increase in serum creatinine. Methotrexate clearance (58-155 ml/min/m2) was significantly (p = 0.007) correlated with GFR, but GFR accounted for only 37% of the variability of methotrexate clearance. CONCLUSIONS:The GFR was normal but highly variable in these children with leukemia and was significantly altered by amphotericin. Our results explain little of the intersubject variability in methotrexate clearance.
journal_name
Pharmacotherapyjournal_title
Pharmacotherapyauthors
Murry DJ,Synold TW,Pui CH,Rodman JHsubject
Has Abstractpub_date
1995-03-01 00:00:00pages
144-9issue
2eissn
0277-0008issn
1875-9114journal_volume
15pub_type
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