Minocycline in acute cerebral hemorrhage an early phase randomized trial

Abdelrahman Y. Fouda, Andrea S. Newsome, Samantha Spellicy, Jennifer L Waller, Wenbo Zhi, David C Hess, Adviye Ergul, David J. Edwards, Susan C. Fagan, Jeffrey A Switzer

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background and Purpose-Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. Methods-This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. Results-A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. Conclusions-In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial.

Original languageEnglish (US)
Pages (from-to)2885-2887
Number of pages3
JournalStroke
Volume48
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Minocycline
Cerebral Hemorrhage
Half-Life
Anti-Inflammatory Agents
Pharmacokinetics
Biomarkers
Stroke
Safety
Protective Agents
Serum
Critical Illness
Hematoma
Oral Administration
Edema
Randomized Controlled Trials

Keywords

  • Biomarkers
  • Critical illness
  • Hematoma
  • Minocycline
  • Neuroprotective agents

ASJC Scopus subject areas

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

Cite this

Minocycline in acute cerebral hemorrhage an early phase randomized trial. / Fouda, Abdelrahman Y.; Newsome, Andrea S.; Spellicy, Samantha; Waller, Jennifer L; Zhi, Wenbo; Hess, David C; Ergul, Adviye; Edwards, David J.; Fagan, Susan C.; Switzer, Jeffrey A.

In: Stroke, Vol. 48, No. 10, 01.10.2017, p. 2885-2887.

Research output: Contribution to journalArticle

Fouda, AY, Newsome, AS, Spellicy, S, Waller, JL, Zhi, W, Hess, DC, Ergul, A, Edwards, DJ, Fagan, SC & Switzer, JA 2017, 'Minocycline in acute cerebral hemorrhage an early phase randomized trial', Stroke, vol. 48, no. 10, pp. 2885-2887. https://doi.org/10.1161/STROKEAHA.117.018658
Fouda, Abdelrahman Y. ; Newsome, Andrea S. ; Spellicy, Samantha ; Waller, Jennifer L ; Zhi, Wenbo ; Hess, David C ; Ergul, Adviye ; Edwards, David J. ; Fagan, Susan C. ; Switzer, Jeffrey A. / Minocycline in acute cerebral hemorrhage an early phase randomized trial. In: Stroke. 2017 ; Vol. 48, No. 10. pp. 2885-2887.
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AU - Newsome, Andrea S.

AU - Spellicy, Samantha

AU - Waller, Jennifer L

AU - Zhi, Wenbo

AU - Hess, David C

AU - Ergul, Adviye

AU - Edwards, David J.

AU - Fagan, Susan C.

AU - Switzer, Jeffrey A

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AB - Background and Purpose-Minocycline is under investigation as a neurovascular protective agent for stroke. This study evaluated the pharmacokinetic, anti-inflammatory, and safety profile of minocycline after intracerebral hemorrhage. Methods-This study was a single-site, randomized controlled trial of minocycline conducted from 2013 to 2016. Adults ≥18 years with primary intracerebral hemorrhage who could have study drug administered within 24 hours of onset were included. Patients received 400 mg of intravenous minocycline, followed by 400 mg minocycline oral daily for 4 days. Serum concentrations of minocycline after the last oral dose and biomarkers were sampled to determine the peak concentration, half-life, and anti-inflammatory profile. Results-A total of 16 consecutive eligible patients were enrolled, with 8 randomized to minocycline. Although the literature supports a time to peak concentration (Tmax) of 1 hour for oral minocycline, the Tmax was estimated to be at least 6 hours in this cohort. The elimination half-life (available on 7 patients) was 17.5 hours (SD±3.5). No differences were observed in inflammatory biomarkers, hematoma volume, or perihematomal edema. Concentrations remained at neuroprotective levels (>3 mg/L) throughout the dosing interval in 5 of 7 patients. Conclusions-In intracerebral hemorrhage, a 400 mg dose of minocycline was safe and achieved neuroprotective serum concentrations. However, oral administration led to delayed absorption in these critically ill patients and should not be used when rapid, high concentrations are desired. Given the safety and pharmacokinetic profile of minocycline in intracerebral hemorrhage and promising data in the treatment of ischemic stroke, intravenous minocycline is an excellent candidate for a prehospital treatment trial.

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KW - Critical illness

KW - Hematoma

KW - Minocycline

KW - Neuroprotective agents

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