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 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 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

Fagan, S. C., Waller, J. L., Nichols, F. T., Edwards, D. J., Pettigrew, L. C., Clark, W., ... Hess, D. C. (2010). Minocycline to Improve Neurologic Outcome in Stroke (MINOS): A dose-finding study. Stroke, 41(10), 2283-2287. https://doi.org/10.1161/STROKEAHA.110.582601

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; Hall, Christiana E.; Switzer, Jeffrey A.; Ergul, Adviye; Hess, David C.

In: Stroke, Vol. 41, No. 10, 10.2010, p. 2283-2287.

Research output: Contribution to journalArticle

Fagan, SC, Waller, JL, Nichols, FT, Edwards, DJ, Pettigrew, LC, Clark, W, Hall, CE, Switzer, JA, Ergul, A & Hess, DC 2010, 'Minocycline to Improve Neurologic Outcome in Stroke (MINOS): A dose-finding study', Stroke, vol. 41, no. 10, pp. 2283-2287. https://doi.org/10.1161/STROKEAHA.110.582601
Fagan SC, Waller JL, Nichols FT, Edwards DJ, Pettigrew LC, Clark W et al. Minocycline to Improve Neurologic Outcome in Stroke (MINOS): A dose-finding study. Stroke. 2010 Oct;41(10):2283-2287. https://doi.org/10.1161/STROKEAHA.110.582601
Fagan, Susan C. ; Waller, Jennifer L. ; Nichols, Fenwick T. ; Edwards, David J. ; Pettigrew, L. Creed ; Clark, Wayne ; 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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