Safety and Tolerability of 619C89 after Acute Stroke
| Autor: | K W, Muir, S J, Hamilton, M W, Lunnon, S, Hobbiger, K R, Lees |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Infarction Disease Piperazines Sodium channel blocker Double-Blind Method Internal medicine Epidemiology Humans Medicine Neurotransmitter Uptake Inhibitors Aged Kidney Dose-Response Relationship Drug business.industry Vascular disease Middle Aged medicine.disease United Kingdom Cerebrovascular Disorders Neuroprotective Agents Pyrimidines Treatment Outcome medicine.anatomical_structure Neurology Anesthesia Acute Disease Cardiology Female Neurology (clinical) Cardiology and Cardiovascular Medicine business Complication Kidney disease |
| Zdroj: | Cerebrovascular Diseases. 8:31-37 |
| ISSN: | 1421-9786 1015-9770 |
| DOI: | 10.1159/000015812 |
| Popis: | Background: 619C89 is a use-dependent sodium channel blocker which reduces hemispheric infarction volume by up to 60% after permanent middle cerebral artery occlusion in rats. Intravenous doses of up to 1 mg/kg have been well tolerated by healthy young and elderly volunteers. This study sought to assess safety and tolerability of 619C89 in the treatment of acute stroke. Methods: Patients were randomised within 12 h of onset of stroke to receive 619C89 or placebo as an intravenous loading dose, followed by maintenance doses given 8 hourly for 64 h in a double-blind, ascending-dose tolerance study. Dosing commenced at 0.5 mg/kg loading plus 0.25 mg/kg/8 h maintenance for the first group and increased in increments of 0.5 mg/kg loading +0.25 mg/kg/8 h maintenance thereafter. Safety evaluation was continued for 3 months. Results: 48 patients were recruited. 12 received placebo and 36 received 619C89 in doses up to 2.5 mg/kg loading plus 1.25 mg/kg/8 h. Dose escalation was stopped after the occurrence of hallucinations in 5 of 18 patients who received 2 mg/kg +1 mg/kg/8 h or more. Gastro-intestinal upset and confusion were also possibly drug related. No drug-related effects on cardiovascular function were found. Conclusions: 619C89 was associated with significant central nervous system side-effects at doses of 2 mg/kg +1 mg/kg/8 h or greater as discrete intravenous infusions within 12 h of stroke onset. It may also cause gastro-intestinal side-effects. Doses below this are well tolerated in patients. No adverse cardiovascular effects were seen. |
| Databáze: | OpenAIRE |
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