Pharmacokinetic Analysis of a Hemodialyzed Patient Treated With Pazopanib.

Pazopanib, an oral multitargeted tyrosine inhibitor, is approved for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) as the first-line treatment. However, no information is available regarding the dosage adjustment of pazopanib for patients undergoing hemodialysis. Therefore, evaluation of the influence of dialysis treatment on pazopanib pharmacokinetics is needed. We examined the effects of hemodialysis on the pharmacokinetics of pazopanib in a patient with RCC. The patient was a 70-year-old man diagnosed with RCC and undergoing hemodialysis. The patient was treated with pazopanib 400 mg daily. On day 3, pazopanib was discontinued due to hepatic dysfunction. Ten days after the cessation of pazopanib (day 13), he was re-challenged with pazopanib using a 200 mg alternate-day regimen. On day 7 after the re-challenge (day 20), the serum trough concentration of pazopanib was 2915 ng/mL (target concentration: >15,000-20,500 ng/mL), and the patient did not show any severe toxicity. Consequently, the pazopanib dosage was increased to 200 mg daily. There was little difference in the area under the concentration-time curve of pazopanib at 200 mg daily between day 34 (off-hemodialysis) and day 35 (on-hemodialysis). The patient developed grade 1 aspartate aminotransferase elevation on day 60, and the pazopanib treatment was discontinued. We show, for the first time, that the pharmacokinetics of pazopanib are rarely affected by hemodialysis, and that dose adjustment is not necessary. However, this case report refers to only 1 patient undergoing hemodialysis, so further studies are needed. (C) 2016 Elsevier Inc. All rights reserved.