Use of the automatic interaction detector method to identify patient characteristics related to methotrexate clearance

Systemic methotrexate (MTX) clearance was determined in 108 children who received 15 courses of MTX, 1000 mg/m 2 iv over 24 hours, as a component of therapy for acute lymphocytic leukemia. The median MTX clearance was used as the representative value for each patient, and these values ranged from 44.7 to 132.1 ml/min/m 2 (X̄ = 78.4 ml/min/m 2 ). The automatic interaction detector approach was used to determine the patient characteristics that correlated with MTX clearance. Characteristics examined were sex, age, estimated Creatinine clearance, SGPT, and body surface area. The initial splits were based on Creatinine clearance, and mean MTX clearances in three subgroups (50 to 100, 100 to 150, and >150 ml/min/m 2 ) were 73.1, 78.3, and 90.5 ml/min/m 2 , respectively. For patients with the slowest Creatinine clearance, abnormal SGPT concentrations (>35 IU/L) were associated with slower MTX clearance (77.6 vs. 67.8 ml/min/m 2 ). In the latter subgroup, boys had faster clearance than girls (77.4 vs. 60.9 ml/min/ m 2 ). These results demonstrate that for children with normal serum Creatinine concentrations, interpatient variability in MTX clearance can partly be explained by measures of renal and hepatic function, which indicates that the observed variability in MTX clearance is not totally random. Clinical Pharmacology and Therapeutics (1986) 39, 592–597; doi: 10.1038/clpt.1986.102