Safety and pharmacokinetics of subcutaneously administered rilonacept in patients with well-controlled end-stage renal disease (ESRD)

J Clin Pharmacol. 2010 Jul;50(7):835-41. doi: 10.1177/0091270009351882. Epub 2009 Dec 24.

Abstract

The safety and pharmacokinetics of a single dose of the IL-1 inhibitor, rilonacept (IL-1 Trap; 160 mg, subcutaneously), was studied in a group of 6 patients with well-controlled end-stage renal disease (ESRD) who were observed for a period of 42 days following dosing. The safety of rilonacept administration was ascertained by regular monitoring of patients for adverse events, by periodic determination of a battery of standard laboratory and hematology tests, and by testing for binding and neutralizing antibodies to rilonacept. Two of the 6 patients had treatment-emergent adverse events that were moderate in intensity and unrelated to administration of rilonacept. There were no deaths, serious adverse events, or withdrawals due to adverse events. No patient developed binding or neutralizing antibodies to rilonacept by the 42nd day postdosing. Mean C(max) estimated by a noncompartmental analysis was 17.2 mg/L; t(max,) 2.80 days; terminal t(1/2), 7.63 days; and AUC(0-infinity), 199.3 d.mg/L. Comparison of these results to those obtained in a population of patients with cryopyrin-associated periodic syndromes, a group of rare, inherited, autoinflammatory disorders (mean [SD] eGFR of 73.1 [13.3] mL/min/1.73m2), shows that ESRD and related hemodialysis procedures do not prolong the elimination of rilonacept, and therefore no dose adjustment should be needed relative to individuals with normal renal function.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Antibodies, Blocking / analysis
  • Area Under Curve
  • Cryopyrin-Associated Periodic Syndromes / complications
  • Female
  • Half-Life
  • Humans
  • Injections, Subcutaneous
  • Kidney Failure, Chronic / metabolism*
  • Linear Models
  • Male
  • Middle Aged
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Recombinant Fusion Proteins / adverse effects*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / pharmacokinetics*
  • Renal Dialysis

Substances

  • Antibodies, Blocking
  • Receptors, Interleukin-1
  • Recombinant Fusion Proteins
  • rilonacept