Pharmacokinetics of Dexrazoxane in Subjects With Impaired Kidney Function

Dexrazoxane is approved as a cardioprotective agent for use in female patients with breast cancer who are receiving doxorubicin. The effect of renal insufficiency on elimination is not known. The pharmacokinetics of dexrazoxane 150 mg/m2, given as a 15‐minute constant‐rate intravenous infusion, were assessed in 24 men and women with varying degrees of renal function in a single‐dose, open‐label, parallel‐group study. Blood and urine samples were measured by a validated liquid chromatography/mass spectrometry assay. Dexrazoxane pharmacokinetic parameters were derived by standard noncompartmental methods. The effect of kidney function and effect of body surface area on the phrmacokinetics of dexrazoxane were analyzed using linear and nonlinear regression in the SPSS statistical program. Dexrazoxane clearance is decreased in subjects with kidney dysfunction. Compared with normal subjects (creatinine clearance [CLCR] >80 mL/min), mean area under the concentration curve from time 0 to infinity (AUC0‐inf) was 2‐fold greater in subjects with moderate (CLCR 30–50 mL/min) to severe (CLCR 80 mL/min). Modeling study results suggested that equivalent exposure could be achieved if dosing was halved in subjects with CLCR less than 40 mL/min compared with controls.