Renal function and methotrexate clearance in children with newly diagnosed leukemia.
Pharmacotherapy
; 15(2): 144-9, 1995.
Article
en En
| MEDLINE
| ID: mdl-7624260
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 MAINRESULTS:
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metotrexato
/
Leucemia-Linfoma Linfoblástico de Células Precursoras
/
Tasa de Filtración Glomerular
Tipo de estudio:
Diagnostic_studies
/
Observational_studies
Límite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Pharmacotherapy
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos