Abstract | BACKGROUND AND PURPOSE: METHODS: An intravenous infusion of dextrorphan or placebo was begun within 48 hours of onset of a mild-to-moderate hemispheric stroke. Initially, patients were treated with either placebo (n = 15) or dextrorphan (n = 22) using a 1-hour loading dose (60 to 150 mg) followed by a 23-hour ascending-dose maintenance infusion (maximum total dose, 3310 mg). Subsequently, 29 patients were treated with dextrorphan in an open trial using a 1-hour loading dose (145 to 260 mg) followed by an 11-hour constant rate (30 to 70 mg/h) infusion. RESULTS: Transient and reversible adverse effects, including nystagmus, nausea, vomiting, somnolence, hallucinations, and agitation, commonly occurred in dextrorphan-treated patients. Loading-dose escalation was stopped because of rapid-onset, reversible, symptomatic hypotension in 7 of 21 patients treated with doses of 200 to 260 mg/h. At the highest rates of maintenance infusion (> 90 mg/h), 3 patients developed deep stupor or apnea. The maximum tolerated loading dose was 180 mg/h, and the maximum tolerated maintenance infusion was 70 mg/h. Maximum plasma levels of 750 to 1000 ng/mL were obtained in 9 patients. There was no difference in neurological outcome at 48 hours between the dextrorphan-treated and placebo-treated patients. CONCLUSIONS: The highest doses of dextrorphan administered were associated with serious adverse experiences in some patients. Lower doses (loading doses of 145 to 180 mg, maintenance infusions of 50 to 70 mg/h) were better tolerated and rapidly produced potentially neuroprotective plasma concentrations of dextrorphan. These doses were associated with well-defined pharmacological effects compatible with N-methyl-D-aspartate receptor antagonism.
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Authors | G W Albers, R P Atkinson, R E Kelley, D M Rosenbaum |
Journal | Stroke
(Stroke)
Vol. 26
Issue 2
Pg. 254-8
(Feb 1995)
ISSN: 0039-2499 [Print] United States |
PMID | 7831698
(Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Acute Disease
- Adult
- Aged
- Brain Ischemia
(drug therapy)
- Cerebrovascular Disorders
(drug therapy)
- Dextrorphan
(adverse effects, pharmacokinetics, therapeutic use)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Humans
- Infusions, Intravenous
- Male
- Middle Aged
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