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141.
142.
Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose-limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule. 相似文献
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BACKGROUND AND PURPOSE: The goals of the present study were to assess the efficacy and safety of nalmefene (Cervene) in patients with acute (< or =6 hours) ischemic stroke and to investigate the safety of combined recombinant tissue plasminogen activator and nalmefene in a separate subset of patients. Nalmefene, an opioid antagonist with relative kappa receptor selectivity, has shown neuroprotective effects in multiple experimental central nervous system injury and ischemic models. Results from an earlier phase II study in patients with acute ischemic stroke suggested that nalmefene was safe and tolerable and may be effective for patients <70 years old. METHODS: This investigation was a phase III, placebo-controlled, double-blind, randomized study of a 24-hour infusion of nalmefene. Patients with acute ischemic stroke who had an onset of symptoms within 6 hours and a baseline score of > or =4 on the NIH Stroke Scale were randomized to receive either 60 mg nalmefene administered as a 10-mg bolus over 15 minutes and then a 50-mg infusion over 23.75 hours or placebo. The primary efficacy outcome was the proportion of patients achieving a score of > or =60 on the Barthel Index and a rating of "moderate disability" or better on the Glasgow Outcome Scale at 12 weeks. Assessments were performed at baseline (predose), hours 12 and 24, days 2 and 7, and week 12. RESULTS: A total of 368 patients were randomized at 42 centers, including 32 patients treated with recombinant tissue plasminogen activator and study drug. Nalmefene was well tolerated. Overall, there was no significant difference in 3-month functional outcome for nalmefene treatment compared with placebo on any of the planned analyses. A prospective secondary analysis also failed to find a treatment effect in patients <70 years old. CONCLUSIONS: Although nalmefene appears to be safe and well tolerated, this study failed to find any treatment benefit in stroke patients treated within 6 hours. 相似文献
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目的在简介磷脂的基础上 ,概括了磷脂类似物和磷脂聚合物的合成方法及其在医药领域中的应用。方法在参阅国内外相关文献的基础上 ,进行分析、整理和归纳。结果磷脂聚合物的合成方法已经发展的比较成熟 ,但是在医药方面的应用主要限于磷脂聚合物型脂质体、聚乙二醇(PEG)修饰型脂质体和磷脂修饰型聚合物。结论具有两亲性和生物相容性的磷脂及其聚合物在医药领域具有广泛的发展前景 相似文献
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149.
目的:探讨患儿苯巴比妥(PB)血清样品在冷处储存的稳定性.方法:荧光偏振免疫法(FPIA)测定30例患儿应用PB治疗时的血药浓度,比较其血清样品当天测定浓度(C1)与其在冷处储存7 d后测定浓度(C7).结果:PB血药浓度C1与C7呈正相关(P<0.01),其回归方程:C7=1.054 5C1-1.275 8,r=0.983 1.平均Re(C7/C1,相当于PB在患儿血清中的平均回收率)为(100.4±4.8)%,RSD为4.70%(n=30),且两者的各组偏差[(C7-C1)/C1]均小于10%.结论:患儿血清样品在冷处储存7 d,其PB能保持稳定,有利于常规治疗药物监测(TDM)时的样品储存. 相似文献
150.
谷氨酸转运体、谷氨酸/胱氨酸转运体与谷氨酸神经细胞毒作用 总被引:9,自引:0,他引:9
谷氨酸转运体与谷氨酸/胱氨酸转运体在脑缺血疾病中起重要作用,谷氨酸转运体的结构或功能改变可使细胞间隙的谷氨酸浓度急剧升高,激活NMDA受体产生一系列的表现,同时抑制谷氨酸/胱氨酸转运体对胱氨酸的摄取,介导谷胱苷肽耗竭、氧自由基升高、胞内钙升高、线粒体损伤、细胞色素c释放等神经细胞毒环节,激活半胱天冬酶诱导凋亡。可进一步加重谷氨酸的神经细胞毒作用。 相似文献