Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer.

Background Epoetin alfa (EPO, PROCRIT®) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy. Procedure Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods. Results Twelve children participated; six (median age 15.2 years; range 9.3–18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0–24 and clearance (CL) were 67.1 IU/ml·hr (13.8–102.6) and 0.26 L/hr/m2 (0.19–1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0–24 and CL of EPO was 126.5 IU/ml·hr (107.3–161.1) and 0.21 L/hr/m2 (0.15–0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects. Conclusions EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects. Pediatr Blood Cancer 2006; 47:572–579. © 2005 Wiley-Liss, Inc.