Minocycline to Improve Neurologic Outcome in Stroke (MINOS): A dose-finding study

Susan C. Fagan, Jennifer L. Waller, Fenwick T. Nichols, David J. Edwards, L. Creed Pettigrew, Wayne M. Clark, Christiana E. Hall, Jeffrey A. Switzer, Adviye Ergul, David C. Hess

Research output: Contribution to journalArticle

159 Scopus citations

Abstract

Background And Purpose-: Minocycline is a promising anti-inflammatory and protease inhibitor that is effective in multiple preclinical stroke models. We conducted an early phase trial of intravenous minocycline in acute ischemic stroke. Methods-: Following an open-label, dose-escalation design, minocycline was administered intravenously within 6 hours of stroke symptom onset in preset dose tiers of 3, 4.5, 6, or 10 mg/kg daily over 72 hours. Minocycline concentrations for pharmacokinetic analysis were measured in a subset of patients. Subjects were followed for 90 days. Results-: Sixty patients were enrolled, 41 at the highest dose tier of 10 mg/kg. Overall age (65±13.7 years), race (83% white), and sex (47% female) were consistent across the doses. The mean baseline National Institutes of Health Stroke Scale score was 8.5±5.8 and 60% received tissue plasminogen activator. Minocycline infusion was well tolerated with only 1 dose limiting toxicity at the 10-mg/kg dose. No severe hemorrhages occurred in tissue plasminogen activator-treated patients. Pharmacokinetic analysis (n=22) revealed a half-life of approximately 24 hours and linearity of parameters over doses. Conclusions-: Minocycline is safe and well tolerated up to doses of 10 mg/kg intravenously alone and in combination with tissue plasminogen activator. The half-life of minocycline is approximately 24 hours, allowing every 24-hour dosing. Minocycline may be an ideal agent to use with tissue plasminogen activator.

Original languageEnglish (US)
Pages (from-to)2283-2287
Number of pages5
JournalStroke
Volume41
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • dose-finding
  • ischemic stroke
  • minocycline
  • neuroprotection
  • pharmacokinetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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