帕拉米韦注射液治疗儿童流感的临床疗效分析

目的探讨儿童流感应用帕拉米韦注射液治疗的临床疗效以及用药安全性。方法随机选定在2016年1月-2019年1月期间佛山市高明区人民医院儿科住院治疗并确诊流感A或B型患儿200例,通过随机数字法将其分为治疗组和对照组。治疗组100例用帕拉米韦注射液治疗,对照组100例用国产磷酸奥司他韦颗粒治疗,评价两组患儿治疗前后症状评分、治疗效果、治疗指标以及不良反应发生情况。结果两组患儿治疗前流感样症状评分无统计学意义(P>0.05),两组患儿治疗后较治疗前流感样症状评分均下降,差异有统计学意义(P<0.05);治疗组治疗后流感样症状评分略小于对照组,但是无统计学意义(P>0.05);治疗组治疗总有效率高于对照组,治疗组患儿发热症状缓解、全部症状缓解以及住院时间均小于对照组,存在统计学意义(P<0.05)。治疗组与对照组不良反应发生率较低,且无统计学意义(P>0.05)。结论帕拉米韦注射液可用于儿童流感治疗,不仅能够保证临床疗效,而且可加快症状缓解,同时存在较高用药安全性。     

Peramivir and laninamivir susceptibility of circulating influenza A and B viruses

Influenza viruses collected from regions of Asia, Africa and Oceania between 2009 and 2012 were tested for their susceptibility to two new neuraminidase inhibitors, peramivir and laninamivir. All viruses tested had normal laninamivir inhibition. However, 3·2% (19/599) of A(H1N1)pdm09 viruses had highly reduced peramivir inhibition (due to H275Y NA mutation) and <1% (6/1238) of influenza B viruses had reduced or highly reduced peramivir inhibition, with single occurrence of variants containing I221T, A245T, K360E, A395E, D432G and a combined G145R+Y142H mutation. These data demonstrate that despite an increase in H275Y variants in 2011, there was no marked change in the frequency of peramivir‐ or laninamivir‐resistant variants following the market release of the drugs in Japan in 2010.     

Mutations I117V and I117M and oseltamivir sensitivity of pandemic (H1N1) 2009 viruses

Analysis of mutations I117V and I117M in the neuraminidase of influenza A pandemic (H1N1) 2009 viruses showed that I117V confers a mild reduction in oseltamivir sensitivity and has a synergistic effect of further increasing resistance when combined with H275Y. Contrary to recent reports, the I117M mutation does not alter oseltamivir sensitivity.     

Peramivir for the treatment of influenza

Peramivir (BioCryst Pharmaceuticals) is a novel investigational intravenous neuraminidase inhibitor that exhibits potent antiviral activity against influenza A and B viruses. Peramivir is created by a structure-based drug design and consists of a cyclopentane backbone with a positively charged guanidinyl group and lipophilic side chains. Peramivir was made available in the USA through the Emergency Investigational New Drug regulations and under an Emergency Use Authorization for hospitalized patients with known or suspected influenza during the 2009 H1N1 influenza pandemic. In trials involving ambulatory adult subjects, intravenous peramivir is safe and has a pharmacokinetic profile that supports once-daily dosing. The drug is licensed in Japan and South Korea and is currently undergoing Phase III trials in the USA. Viral resistance mechanisms to peramivir have not been fully delineated and ongoing surveillance is important. Given the serious health threat of influenza at all ages and limitations in vaccine delivery, peramivir is a promising addition to the currently limited treatment options for the treatment of severe influenza infection.     

Peramivir获准紧急用于H1N1的治疗

FDA已于近期批准BioCryst制药公司开发的神经氨酸酶抑制剂peramivir用于H1N1流感的紧急治疗,并已将其列入与H1N1流感爆发有关的突发公共卫生事件的应急措施清单,与H1N1疫苗及已批准的抗病毒药--罗氏公司的达菲(奥塞米韦)和葛兰素史克公司的Relenza(扎那米韦)共同用于H1N1的防治.     

Improvement of respiratory symptoms and health‐related quality of life with peramivir in influenza patients with chronic respiratory disease: Additional outcomes of a randomized,open‐label study

BackgroundTo compare peramivir 300 mg single‐dose, peramivir 600 mg repeat‐dose, and oseltamivir effects on health‐related quality of life, including respiratory symptoms and general conditions, time to symptom alleviation, time to fever resolution, incidence of exacerbations, and virus titer, in influenza patients with chronic respiratory disease.MethodsWe report additional outcomes from a 2‐week, multicenter, randomized, open‐label study in Japan (UMIN000030118). Influenza patients with chronic respiratory disease received intravenous peramivir (300 mg single‐dose [n = 66], 600 mg repeat‐dose [600 mg/d of 2 consecutive days; n = 70]) or oral oseltamivir (75 mg twice daily, 5 days; n = 72). The principal endpoint of this analysis was change from baseline to Day 14 at each time point in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) scores.ResultsBoth peramivir regimens reduced total CAT score at Day 3 more than oseltamivir (peramivir 600 mg vs oseltamivir, P = .0032; peramivir 300 mg vs oseltamivir, P = .0203). Cough/phlegm CAT scores were most improved with peramivir 600 mg. Median time to alleviation of three respiratory symptoms was longer with peramivir 600 mg (68.9 hours) than with peramivir 300 mg (50.6 hours, hazard ratio [HR] 1.57; P = .0191) and shorter with peramivir 300 mg than oseltamivir (78.8 hours, HR 0.62; P = .0141). Alleviation of seven influenza symptoms and fever resolution was shortest with peramivir 300 mg.ConclusionsRapid improvement in CAT score, including cough, and shorter time to alleviation of respiratory symptoms associated with peramivir is of potential benefit to patients with chronic respiratory disease.     

Neuraminidase inhibitor susceptibility testing in human influenza viruses: a laboratory surveillance perspective

Neuraminidase inhibitors (NAIs) are vital in managing seasonal and pandemic influenza infections. NAI susceptibilities of virus isolates (n = 5540) collected during the 2008-2009 influenza season were assessed in the chemiluminescent neuraminidase inhibition (NI) assay. Box-and-whisker plot analyses of log-transformed IC(50)s were performed for each virus type/subtype and NAI to identify outliers which were characterized based on a statistical cutoff of IC(50) >3 interquartile ranges (IQR) from the 75(th) percentile. Among 1533 seasonal H1N1 viruses tested, 1431 (93.3%) were outliers for oseltamivir; they all harbored the H275Y mutation in the neuraminidase (NA) and were reported as oseltamivir-resistant. Only 15 (0.7%) of pandemic 2009 H1N1 viruses tested (n = 2259) were resistant to oseltamivir. All influenza A(H3N2) (n = 834) and B (n = 914) viruses were sensitive to oseltamivir, except for one A(H3N2) and one B virus, with D151V and D197E (D198E in N2 numbering) mutations in the NA, respectively. All viruses tested were sensitive to zanamivir, except for six seasonal A(H1N1) and several A(H3N2) outliers (n = 22) which exhibited cell culture induced mutations at residue D151 of the NA. A subset of viruses (n = 1058) tested for peramivir were sensitive to the drug, with exception of H275Y variants that exhibited reduced susceptibility to this NAI. This study summarizes baseline susceptibility patterns of seasonal and pandemic influenza viruses, and seeks to contribute towards criteria for defining NAI resistance.     

衍生化LC-MS/MS测定大鼠血浆中新型抗流感药物帕拉米韦及其在药代动力学研究中的应用

目的：建立灵敏、可靠的衍生化LC-MS/MS新方法测定大鼠血浆中帕拉米韦的浓度。方法：血浆样品前处理包括蛋白沉淀和用盐酸（10mol/L）-甲醇（10：90,体积比）为衍生化试剂的衍生化反应,测定采用LC-MS/MS。通过电喷雾电离源以选择反应监测（SRM）方式进行正离子检测,用于定量分析的离子反应分别为m/z343→284（帕拉米韦衍生物）和m/z299→152（内标Ro64-0802衍生物）。色谱分离采用ZorbaxRX-C8柱（2.1mm×150mm,5μm）,以乙腈-水-甲酸（30：70：0.1,体积比,0.2ml/min）为流动相。结果：测定帕拉米韦的线性范围为10～10000ng/ml,相关系数r2为0.9940,定量下限为10ng/ml,批内和批间RSD%分别在5.0%和7.1%以内,准确度控制在89.9%～106.1%。结论：本方法通过衍生化反应,使帕拉米韦保留时间增加,基质抑制降低并使检测灵敏度提高。该方法成功应用于帕拉米韦非临床和临床研究中。     

帕拉米韦氯化钠注射液治疗儿童流行性感冒的效果及安全性

目的探讨帕拉米韦氯化钠注射液治疗儿童流行性感冒(流感)的效果及安全性,为临床安全用药提供依据。方法选取2017年1月—2018年12月涿州市医院收治的流感患儿260例,按照随机数字表法将其分为观察组(n=130)和对照组(n=130)。对照组给予磷酸奥司他韦颗粒治疗,观察组给予帕拉米韦氯化钠注射液治疗,观察2组的疗效及安全性。结果观察组治疗后的体温恢复正常时间、咳嗽缓解时间、鼻卡他/鼻塞缓解时间、咽喉痛缓解时间及症状完全缓解时间均明显低于对照组,差异有统计学意义(P均0.05)。观察组治疗后的总有效率明显高于对照组(96.2%vs. 83.8%,P 0.05)。观察组治疗前后血常规各项指标与对照组比较,差异均无统计学意义(P均 0.05)。观察组与对照组治疗后不良反应发生率比较,差异无统计学意义(8.5%vs. 12.3%,P 0.05)。结论采用帕拉米韦氯化钠治疗儿童流感的效果较好,能更快地改善流感症状,且不会增加不良反应。