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

141 Citations (Scopus)

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 1 2010

Fingerprint

Minocycline
Nervous System
Stroke
Tissue Plasminogen Activator
Half-Life
Pharmacokinetics
National Institutes of Health (U.S.)
Protease Inhibitors
Anti-Inflammatory Agents
Hemorrhage

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Minocycline to Improve Neurologic Outcome in Stroke (MINOS) : A dose-finding study. / Fagan, Susan C.; Waller, Jennifer L; Nichols, Fenwick T; Edwards, David J.; Pettigrew, L. Creed; Clark, Wayne M.; Hall, Christiana E.; Switzer, Jeffrey A; Ergul, Adviye; Hess, David C.

In: Stroke, Vol. 41, No. 10, 01.10.2010, p. 2283-2287.

Research output: Contribution to journalArticle

Fagan, Susan C. ; Waller, Jennifer L ; Nichols, Fenwick T ; Edwards, David J. ; Pettigrew, L. Creed ; Clark, Wayne M. ; Hall, Christiana E. ; Switzer, Jeffrey A ; Ergul, Adviye ; Hess, David C. / Minocycline to Improve Neurologic Outcome in Stroke (MINOS) : A dose-finding study. In: Stroke. 2010 ; Vol. 41, No. 10. pp. 2283-2287.
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