Pharmacokinetics and safety of sunitinib malate in subjects with impaired renal function.

Abstract

This phase I, open-label, single-dose study evaluates the effects of severe renal impairment and end-stage renal disease (ESRD) requiring hemodialysis on the pharmacokinetics, safety, and tolerability of sunitinib and its primary active metabolite, SU12662. Subjects with normal renal function (creatinine clearance > 80 mL/min), severe renal impairment (creatinine clearance < 30 mL/min), and ESRD requiring hemodialysis receive a single dose of sunitinib 50 mg. Serial blood samples are collected for quantification of plasma concentrations using a validated liquid chromatography with tandem mass spectrometry assay. Safety is monitored. Twenty-four subjects complete the study. Pharmacokinetics in subjects with severe renal impairment appear similar to those with normal renal function. Plasma exposure to sunitinib and SU12662 appears lower in subjects with ESRD compared with subjects with normal renal function or severe renal impairment. Single-dose sunitinib 50 mg is well tolerated regardless of renal function. The currently approved starting dose of sunitinib 50 mg on Schedule 4/2 is expected to be appropriate for patients with renal impairment; any subsequent dose modifications should be based on patients' ability to tolerate treatment.

• Authors: Reza Khosravan, Melvin Toh, May Garrett, Joann La Fargue, Grace Ni, Thomas C Marbury, Suzanne K Swan, Norman M Lunde, Carlo L Bello
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 50 Issue 4 Pg. 472-81 (Apr 2010) ISSN: 1552-4604 [Electronic] England
• PMID: 19779038 (Publication Type: Clinical Trial, Phase I, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Pyrroles
• Sunitinib

Topics

• Adult
• Aged
• Female
• Follow-Up Studies
• Humans
• Indoles (adverse effects, pharmacokinetics)
• Kidney Failure, Chronic (drug therapy, metabolism, physiopathology)
• Kidney Function Tests
• Male
• Metabolic Clearance Rate (drug effects, physiology)
• Middle Aged
• Pyrroles (adverse effects, pharmacokinetics)
• Sunitinib