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

151 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
Publication statusPublished - Oct 1 2010

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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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