帕拉米韦治疗心功能不全儿童流感的疗效及安全性

目的 观察帕拉米韦在治疗患有心功能不全疾病儿童流感的临床疗效及安全性.方法 采用前瞻性研究方法,将2016年1月-2017年1月北京儿童医院心内科收治的患有心功能不全疾病同时确诊流感的患儿,以是否自愿接受帕拉米韦氯化钠注射液输液治疗分为治疗组和对照组,所有病例均进行常规对症治疗,比较两组间发热缓解时间、症状缓解时间、不良反应、并发症、抗生素使用等.结果 治疗组30例,对照组30例.治疗组和对照组平均发热缓解时间分别为(19.9±10.6)h和(57.6±33.7)h,平均症状缓解时间分别为(39.9±39.8)h和(60.7±33.3)h,治疗组发热及咳嗽、咽喉痛、鼻卡他/鼻塞等主要症状缓解时间显著少于对照组(P＜0.05).治疗组和对照组并发症发生率为分别为10.0％(3/30)和40.0％(12/30),抗菌药物使用率分别为30.0％(9/30)和66.7％(20/30),治疗组并发症及抗菌药物使用率和使用天数显著少于对照组(P＜0.05).治疗组与对照组药物平均每例使用总费用分别为658元和792元,差异无统计学意义(P＞0.05).结论 在患有心功能不全的患儿流感发病后使用帕拉米韦可以显著缩短发热缓解时间,快速缓解症状,减少并发症和抗菌药物使用,不增加药物使用总费用.     

In vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011–2012 season in Japan

The neuraminidase inhibitors oseltamivir phosphate (Tamiflu^®), zanamivir (Relenza^®), laninamivir octanoate (Inavir^®), and peramivir (Rapiacta^®) have been available for the treatment of influenza in Japan since 2010. To assess the extent of viral resistance, we measured the 50% inhibitory concentration (IC₅₀) of each drug for influenza virus isolates from the 2011–2012 influenza season.Specimens were obtained from patients prior to treatment. Viral isolation was done using Madine-Darby canine kidney cells, and the type and subtype of influenza A(H1N1)pdm09, A(H3N2), or influenza B were determined by RT-PCR using type- and subtype-specific primers. The IC₅₀ was determined by a neuraminidase inhibition assay using a fluorescent substrate. The lineage of influenza B virus was determined by direct sequencing of the hemagglutinin gene.Influenza A(H3N2) and influenza B viruses were isolated in 283 and 42 patients, respectively, while no influenza A(H1N1)pdm09 virus was isolated. No isolate showed an IC₅₀ value exceeding 50 nM for any of the neuraminidase inhibitors. IC₅₀ values for A(H3N2) were similar between the 2010–2011 and 2011–2012 seasons. In contrast, the IC₅₀ values for influenza B viruses in the 2011–2012 season to the four drugs were significantly lower than those found in the 2010–2011 season. These results indicate that the currently epidemic influenza viruses are susceptible to all four neuraminidase inhibitors, with no trend for IC₅₀ values to increase in Japan at present.     

帕拉米韦对比奥司他韦治疗儿童流感的系统评价和药物经济性分析

目的：系统评价帕拉米韦对比奥司他韦治疗儿童流感有效性和安全性,为临床治疗提供循证参考。方法：计算机检索中英文数据库,检索帕拉米韦对比奥司他韦治疗儿童流感的随机对照研究（RCT）,筛选文献、提取资料,并评价纳入研究的偏倚风险后,采用RevMan5.3软件进行Meta分析,并采用Tree Age Pro 2011软件运用决策树模型进行药物成本-效用分析。结果：共纳入17个RCT,合计2992例患者。Meta分析结果显示：①帕拉米韦组发热时间[MD=1.14,95%Cl（1.11,1.17）]显著低于奥司他韦组;②帕拉米韦组治疗有效率[MD=1.14,95%Cl（1.11,1.17）]显著高于奥司他韦组;③帕拉米韦组不良反应发生率[RR=0.65,95%Cl（0.54,0.79）]显著低于奥司他韦组。药物经济性研究发现,帕拉米韦对比奥司他韦的增量成本-效用比（ICER）为5719.95元,即帕拉米韦每增加1%的平均有效率较奥司他韦需额外花费5719.95元。结论：帕拉米韦在治疗儿童流感的有效性和安全性方面优于奥司他韦,在经济性评价中,以此药“药到病除”,当支付阈值高于5719.95元时,帕拉米韦增加的成本完全值得。     

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): A drug use investigation

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings.     

HPLC法测定帕拉米韦的含量及其有关物质

建立帕拉米韦含量及有关物质的HPLC测定方法。色谱柱:Agilent Zorbax SB C18(250 mm×4.6 mm,5μm);流动相:含0.1%三乙胺的0.005 mol·L-1磷酸二氢钾溶液(pH 6.0)-乙腈(93∶7);检测波长:210 nm。     

小儿豉翘清热颗粒联合帕拉米韦治疗儿童流行性感冒的临床研究

目的探讨小儿豉翘清热颗粒联合帕拉米韦氯化钠注射液治疗儿童流行性感冒的临床疗效。方法回顾性分析2019年9月—2020年9月漯河市第三人民医院收治的108例流行性感冒患儿的临床资料,根据住院号的奇偶性分为对照组和治疗组,每组各54例。对照组静脉滴注帕拉米韦氯化钠注射液,10 mg/kg,1次/d。治疗组在对照组基础上口服小儿豉翘清热颗粒,1～3岁患儿2～3 g/次;4～6岁3～4 g/次;7～9岁4～5 g/次;10岁以上6 g/次,3次/d。两组患儿均治疗7 d。观察两组患者临床疗效,比较治疗前后两组患者临床症状消失时间及血清超敏C反应蛋白(hs-CRP)、巨噬细胞迁移抑制因子(MIF)、高迁移率族蛋白B-1(HMGB-1)、血红素氧合酶-1(HO-1)和半胱氨酰白三烯(CYSLTS)水平。结果治疗后,对照组总有效率为84.91%,显著低于治疗组的98.15%(P0.05)。治疗后,治疗组患者临床症状消失时间明显早于对照组(P0.05)。治疗后,两组患儿血清hs-CRP、MIF、HMGB1、CYSLTS水平明显降低,而HO-1水平明显升高(P0.05);治疗后,且治疗组这些血清学指标明显好于对照组(P0.05)。结论小儿豉翘清热颗粒联合帕拉米韦治疗儿童流行性感冒可显著改善临床症状,降低机体炎症反应,具有一定的临床推广应用价值。     

Clinical effectiveness of four neuraminidase inhibitors (oseltamivir,zanamivir, laninamivir,and peramivir) for children with influenza A and B in the 2014–2015 to 2016–2017 influenza seasons in Japan

The clinical effectiveness of four neuraminidase inhibitors (NAIs) (oseltamivir, zanamivir, laninamivir, and peramivir) for children aged 0 months to 18 years with influenza A and B were investigated in the 2014–2015 to 2016–2017 influenza seasons in Japan. A total of 1207 patients (747 with influenza A and 460 with influenza B) were enrolled. The Cox proportional-hazards model using all of the patients showed that the duration of fever after administration of the first dose of the NAI was shorter in older patients (hazard ratio = 1.06 per 1 year of age, p < 0.001) and that the duration of fever after administration of the first dose of the NAI was shorter in patients with influenza A infection than in patients with influenza B infection (hazard ratio = 2.21, p < 0.001). A logistic regression model showed that the number of biphasic fever episodes was 2.99-times greater for influenza B-infected patients than for influenza A-infected patients (p < 0.001). The number of biphasic fever episodes in influenza A- or B-infected patients aged 0–4 years was 2.89-times greater than that in patients aged 10–18 years (p = 0.010), and the number of episodes in influenza A- or B-infected patients aged 5–9 years was 2.13-times greater than that in patients aged 10–18 years (p = 0.012).     

帕拉米韦对比奥司他韦治疗流行性感冒合并热性惊厥患儿的药物经济学评价

目的:比较帕拉米韦和奥司他韦治疗流行性感冒(简称流感)合并热性惊厥患儿的有效性和经济性。方法:采用回顾性研究方法,收集2018年12月-2019年3月我院收治的152例流感合并热性惊厥的住院患儿,根据其用药情况分为帕拉米韦组81例,奥司他韦组71例。比较两组患儿的发热缓解时间、用药天数、住院天数、临床效果(以抽搐、咳嗽、鼻塞、流涕、咽痛等进行判定)、皮疹发生率和联用抗生素、中药的患儿例数。采用成本-效果分析法评价两组患儿用药方案的成本-效果比(CER)和增量成本-效果比(ICER)。通过下调15%的药品价格重新计算CER和ICER的方法以及采用有序Logistic回归对效果和多元线性回归对总成本进行敏感性分析。结果:两组患儿的发热缓解时间、用药天数、住院天数、皮疹发生率和联用抗生素患儿占比差异均无统计学意义(P>0.05),但联用中药患儿占比和临床效果差异有统计学意义,帕拉米韦组联用中药患儿占比显著低于奥司他韦组(P<0.001),临床效果显著优于奥司他韦组(P=0.021)。帕拉米韦组和奥司他韦组的总成本分别为5 442.84元/人和5 571.71元/人(P=0.795)、CER分别为54.47和56.51,帕拉米韦组的ICER为-89.38。敏感性分析结果与基础分析结果一致。结论:与奥司他韦相比,帕拉米韦治疗流感合并热性惊厥患儿的效果更好,成本更低。     

高效液相色谱法测定不同时间人血浆中帕拉米韦的浓度及临床观察

目的 测定帕拉米韦给药后不同时间人血浆中的药物浓度,观察病人用药后安全性及疗效,为临床使用帕拉米韦提供依据.方法 高效液相色谱(HPLC)法测定帕拉米韦的血药浓度,以5 mmol/L磷酸二氢钾溶液(0.1％三乙胺)-乙腈为流动相,磷酸调pH 5.0;检测波长210 nm;流速1.0 mL/min;用药后对病人进行安全性随访.结果 血浆中无干扰测定的内源性物质,线性范围为1～50μg/mL,最低定量限(LLOQ)为1μg/mL,回收率102.5％～110.4％,日间精密度及稳定性均良好,5例病人不同时间血浆中的帕拉米韦均可检出;5例病人的发热缓解时间分别为33、26、26、48、54 h,流感症状缓解时间分别为89、>120、28、48、54 h,发生1例不良反应.结论 HPLC检测方法可靠,适用于人血浆中帕拉米韦的测定.帕拉米韦能快速缓解流感症状,虽然出现的不良事件为轻度,但也要监测其不良反应,以保证用药安全性及有效性.