Affordable Access

Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study

Authors
Publisher
International Society for Cerebral Blood Flow & Metabolism, Inc.
Publication Date
Disciplines
  • Medicine
  • Pharmacology

Abstract

Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study Intravenous anakinra can achieve experimentally effective concentrations in the central nervous system within a therapeutic time window: results of a dose-ranging study James Galea1,2, Kayode Ogungbenro3, Sharon Hulme1, Andrew Greenhalgh2, Leon Aarons3, Sylvia Scarth1, Peter Hutchinson4, Samantha Grainger4, Andrew King1, Stephen J Hopkins1, Nancy Rothwell2 and Pippa Tyrrell1 1Brain Injury Research Group, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford, UK; 2Faculty of Life Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK; 3Pharmacometrics Research Group, Manchester Academic Health Sciences Centre, Centre for Applied Pharmacokinetics Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK; 4Department of Neurosurgery, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK The naturally occurring antagonist of interleukin-1, IL-1RA, is highly neuroprotective experimentally, shows few adverse effects, and inhibits the systemic acute phase response to stroke. A single regime pilot study showed slow penetration into cerebrospinal fluid (CSF) at experimentally therapeutic concentrations. Twenty-five patients with subarachnoid hemorrhage (SAH) and external ventricular drains were sequentially allocated to five administration regimes, using intravenous bolus doses of 100 to 500mg and 4hours intravenous infusions of IL-1RA ranging from 1 to 10mg per kg per hour. Choice of regimes and timing of plasma and CSF sampling was informed by pharmacometric analysis of pilot study data. Data were analyzed using nonlinear mixed effects modeling. Plasma and CSF concentrations of IL-1RA in all regimes were within the predicted intervals. A 500-mg bolus followed by an intraveno

There are no comments yet on this publication. Be the first to share your thoughts.