{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:20:39Z","timestamp":1776450039765,"version":"3.51.2"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2001,3]]},"abstract":"<jats:p>\n            <jats:italic>Background and Purpose<\/jats:italic>\n            \u2014Increased free radical formation contributes to the damage caused to the brain by acute ischemia. NXY-059 is a nitrone-based free radical trapping agent in development for acute stroke. NXY-059 has neuroprotective efficacy when given 5 hours after onset of transient focal ischemia in the rat.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods<\/jats:italic>\n            \u2014This was a randomized, double-blind, placebo-controlled, parallel group, multicenter study that evaluated the safety and tolerability of 2 NXY-059 dosing regimens compared with placebo within 24 hours of acute stroke. NXY-059 was administered as either 250 mg over 1 hour followed by 85 mg\/h for 71 hours or 500 mg over 1 hour followed by 170 mg\/h for 71 hours; plasma concentrations were monitored. Neurological and functional outcomes were recorded up to 30 days.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Results<\/jats:italic>\n            \u2014One hundred fifty patients were recruited, of whom 147 received study treatments and completed assessments (50 placebo, 48 lower-dose NXY-059, 49 higher-dose NXY-059). Mean (\u00b1SD) age was 68 (\u00b110) years, and baseline National Institutes of Health Stroke Scale score was 7.9 (\u00b16.2). Serious adverse events occurred in 16%, 23%, and 16% of patients, respectively, with deaths in 0%, 10%, and 4%, largely following the proportions with primary intracerebral hemorrhage (6%, 16%, and 8%). Hyperglycemia, headache, and fever were common but not related to treatment. The mean unbound steady state NXY-059 plasma concentrations were 25 and 45 \u03bcmol\/L, respectively. Population pharmacokinetic analysis estimated clearance to be 4.6 L\/h.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014NXY-059 was well tolerated in patients with an acute stroke. The testing of higher doses in future trials may be justified.\n          <\/jats:p>","DOI":"10.1161\/01.str.32.3.675","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:10:52Z","timestamp":1308341452000},"page":"675-680","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":70,"title":["Tolerability and Pharmacokinetics of the Nitrone NXY-059 in Patients With Acute Stroke"],"prefix":"10.1161","volume":"32","author":[{"given":"K. R.","family":"Lees","sequence":"first","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Barer","sequence":"additional","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. A.","family":"Ford","sequence":"additional","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Kostulas","sequence":"additional","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.-F.","family":"Cheng","sequence":"additional","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Odergren","sequence":"additional","affiliation":[{"name":"From the University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK (K.R.L.); Department of Medicine for the Elderly, University Hospital Aintree, Liverpool, UK (A.K.S.); Stroke Research Team, Queen Elizabeth Hospital, Gateshead, UK (D.B.); Wolfson Unit of Clinical Pharmacology, Department of Pharmacological Sciences, University of Newcastle-upon-Tyne, Newcastle, UK (G.A.F.); Department of Neurology, Huddinge University Hospital, Huddinge, Sweden (V.K.); and AstraZeneca..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1258\/0007142001903030"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.9.1151"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000015847"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.31.2.347"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.1.21"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02326-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200005000-00002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200005000-00003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.9.1453"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000007962"},{"key":"e_1_3_2_12_2","first-page":"2259","volume":"30","year":"1999","unstructured":"IMAGES Study Group. 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