Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study.
Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study.
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DOI：
10.1161/strokeaha.110.582601
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发表时间：
2010-10
期刊：
影响因子：
8.3
通讯作者：
Hess DC
中科院分区：
文献类型：
--
作者：
Fagan SC;Waller JL;Nichols FT;Edwards DJ;Pettigrew LC;Clark WM;Hall CE;Switzer JA;Ergul A;Hess DC
米诺环素是一种有前途的抗炎和蛋白酶抑制剂，在多种临床前卒中模型中有效。我们进行了一项静脉注射米诺环素治疗急性缺血性卒中的早期试验。按照开放标签、剂量递增设计，在卒中症状发作后6小时内静脉给予米诺环素，预设剂量等级为3、4.5、6或10 mg/kg/天，持续72小时。在一部分患者中测量米诺环素浓度以进行药代动力学分析。受试者随访90天。入组了60例患者，其中41例接受最高剂量10 mg/kg。各剂量组的总体年龄（65±13.7）、人种（83%白色）和性别（47%女性）一致。平均基线NIHSS为8.5±5.8，60%接受tPA治疗。米诺环素输注耐受性良好，在10 mg/kg剂量下仅出现1次剂量限制性毒性。在tPA治疗的患者中没有发生严重的脑血管病。药代动力学分析（n=22）显示半衰期约为24小时，参数随剂量呈线性。1.）的人。米诺环素在高达10 mg/kg IV单独给药和与tPA联合给药时安全且耐受性良好。2.）的情况。米诺环素的半衰期约为24小时，允许每24小时给药一次。3.）第三章米诺环素可能是与tPA联合使用的理想药物。
Minocycline is a promising anti-inflammatory and protease inhibitor that is effective in multiple pre-clinical stroke models. We conducted an early phase trial of intravenous (IV) minocycline in acute ischemic stroke. Following an open label, dose escalation design, minocycline was administered IV 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. Sixty patients were enrolled, 41 at the highest dose tier of 10 mg/kg. Overall age (65±13.7), race (83% white) and sex (47% female) were consistent across the doses. The mean baseline NIHSS was 8.5±5.8 and 60% received tPA. Minocycline infusion was well tolerated with only 1 dose limiting toxicity at the 10 mg/kg dose. No severe hemorrhages occurred in tPA treated patients. Pharmacokinetic analysis (n=22) revealed a half life of about 24 hours and linearity of parameters over doses. 1.) Minocycline is safe and well tolerated up to doses of 10 mg/kg IV alone and in combination with tPA. 2.) The half life of minocycline is about 24 hours, allowing every 24 hour dosing. 3.) Minocycline may be an ideal agent to use with tPA.