This study analyzed case and prescription data of children aged 12 to 18 years diagnosed with influenza A from the outpatient and emergency departments at the Women and Children’s Hospital of Ningbo University during...This study analyzed case and prescription data of children aged 12 to 18 years diagnosed with influenza A from the outpatient and emergency departments at the Women and Children’s Hospital of Ningbo University during the influenza epidemic period between February and April 2023.Patients were categorized into two groups based on their medication:the Baloxavir Marboxil group(196 cases)and the Oseltamivir group(126 cases).SPSS Statistics 24.0 software was utilized to compare variables between the two groups,including age,sex,weight,first visit department,number of visits,average prescription cost per patient,drug varieties used,hospitalization rate,and the combined medication usage,to evaluate the relative advantages and disadvantages of the two treatments.The results indicated that the number of visits in the Baloxavir Marboxil group was significantly lower than in the Oseltamivir group,whereas the average prescription cost per patient was higher(P<0.05).There were no significant differences between the two groups regarding age,sex,weight,first visit department,number of drug types used,hospitalization rate,or combined medication usage(P>0.05).When comparing the use of single-class combined drugs,only the quantity of antiviral drugs differed significantly(P<0.05).The Oseltamivir group required more adjuvant treatment with both Chinese and Western antiviral medications.The distribution of the number of combined drug types was concentrated around three and two types in both groups(Baloxavir Marboxil group:41.34%and 39.66%;Oseltamivir group:44.54%and 36.97%).This study highlighted that the new drug,Baloxavir Marboxil,offered certain therapeutic benefits over Oseltamivir in treating influenza among children aged 12 to 18 years,including advantages in single-dose administration,oral compliance,and specific treatment outcomes.The higher unit cost associated with Baloxavir Marboxil might be a factor for further consideration.These findings provided a new reference point for the clinical selection of anti-influenza medications.展开更多
流行性感冒发病率高,传染性强,且流感并发症的发病率和死亡率最高。2018年10月,美国食品药品管理局(Food and Drug Administration,FDA)加速批准新型的帽依赖性核酸内切酶抑制剂baloxavir marboxil上市,用于治疗12岁及以上有流感症状且...流行性感冒发病率高,传染性强,且流感并发症的发病率和死亡率最高。2018年10月,美国食品药品管理局(Food and Drug Administration,FDA)加速批准新型的帽依赖性核酸内切酶抑制剂baloxavir marboxil上市,用于治疗12岁及以上有流感症状且不超过48 h的急性单纯型流感患者。临床研究显示,baloxavir marboxil对流感有较好的客观缓解率。本文对其药理作用、临床评价、安全性及用法用量等进行简要概述。展开更多
巴洛沙韦玛波西酯(baloxavir marboxil)是近20年来首创的新作用机制的抗流行性感冒(流感)病毒新药,由日本盐野义(Shionogi)制药株式会社首先研制,作用于流感病毒基因组转录所必需的聚合酶酸性蛋白的内切酶,对甲型和乙型流感病毒均有很...巴洛沙韦玛波西酯(baloxavir marboxil)是近20年来首创的新作用机制的抗流行性感冒(流感)病毒新药,由日本盐野义(Shionogi)制药株式会社首先研制,作用于流感病毒基因组转录所必需的聚合酶酸性蛋白的内切酶,对甲型和乙型流感病毒均有很强的抑制活性。日本厚生省新药审批部门:日本医药品医疗器械综合机构(Pharmaceuticals and Medical Devices Agency,PMDA)于2015年11月给予该公司单剂治疗≥12岁、无并发症的急性流感优先评审待遇,2018年2月予以加速许可,用于治疗甲型和乙型流感,并于2018年2月23日批准上市,商品名为Xofluza~®。2016年2月盐野义制药公司与瑞士罗氏制药公司签署合作协议,授予罗氏公司除日本和中国台湾地区之外的全球开发与经营权,只保留在美国共同开发权。瑞士罗氏制药集团公司属下的基因泰克(Genentech)制药公司于2018年6月26日获得美国食品药品监督管理局(FDA)优先审评资格,并于2018年10月24日获准上市,商品名为Xofluza~®。该文对巴洛沙韦玛波西酯的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。展开更多
Baloxavir marboxil is a polymerase acidic(PA)endonuclease inhibitor,which is approved by the U.S Food and Drug Administration(FDA)on October 25,2018,for the treatment of uncomplicated influenza patients aged 12 years ...Baloxavir marboxil is a polymerase acidic(PA)endonuclease inhibitor,which is approved by the U.S Food and Drug Administration(FDA)on October 25,2018,for the treatment of uncomplicated influenza patients aged 12 years and older.In the present work,we reviewed the pharmacodynamics,pharmacokinetics,drug interactions,clinical trials and adverse reactions of baloxavir marboxil.展开更多
目的系统评价玛巴洛沙韦治疗儿童流行性感冒的有效性和安全性。方法检索PubMed、Embase、Web of Science、Cochrane Library、中国生物医学文献数据库、中国知网、万方和维普等数据库,检索时间为建库至2023年11月15日,选取关于玛巴洛沙...目的系统评价玛巴洛沙韦治疗儿童流行性感冒的有效性和安全性。方法检索PubMed、Embase、Web of Science、Cochrane Library、中国生物医学文献数据库、中国知网、万方和维普等数据库,检索时间为建库至2023年11月15日,选取关于玛巴洛沙韦治疗儿童流感病毒感染的随机对照试验和队列研究,分别采用Cochrane风险偏倚评价工具和纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)进行文献质量评价,采用Rev‐Man 5.3软件进行Meta分析。结果共纳入11篇文献,包括3篇随机对照试验和8篇队列研究。与神经氨酸酶抑制剂(奥司他韦、扎那米韦、帕拉米韦和拉尼米韦)相比,玛巴洛沙韦治疗乙型流感的中位发热持续时间较短(17.0 h vs.48.3 h,P<0.01)。与奥司他韦相比,在甲流和乙流亚组中,玛巴洛沙韦组发热持续时间(甲流:MD=-6.30,95%CI:-10.12~-2.49,P=0.001;乙流:MD=-26.94,95%CI:-47.11~-6.77,P=0.009)、症状持续时间[甲流:MD=-11.13,95%CI:-19.34~-2.93,P=0.008;乙流:(4.9±1.3)d vs.(5.4±2.4)d,P<0.01]均更短;在甲流亚组中,玛巴洛沙韦组的中位病毒清除率(单位:log10拷贝数/d)更高[0.81(0.52,1.12)vs.0.63(0.44,0.93),P=0.007];玛巴洛沙韦组复诊率更低(8.05%vs.24.84%,P<0.001)。与扎那米韦相比,玛巴洛沙韦的中位病毒清除率(单位:log10拷贝数/d)差异无统计学意义[甲流:0.81(0.52,1.12)vs.0.90(0.65,1.08),P>0.05;乙流:0.77(0.38,1.04)vs.0.55(0.27,0.77),P>0.05]。与拉尼米韦相比,玛巴洛沙韦的中位病毒清除率(单位:log10拷贝数/d)[甲流:0.81(0.52,1.12)vs.0.76(0.45,1.06),P>0.05;乙流:0.77(0.38,1.04)vs.0.37(0.29,0.56),P>0.05]、复诊率差异无统计学意义(8.05%vs.12.35%,P=0.79)。在安全性方面,玛巴洛沙韦与奥司他韦相比,药物相关不良事件发生率更低(OR=0.66,95%CI:0.44~0.98,P<0.05),总不良事件发生率差异无统计学意义(OR=0.85,95%CI:0.69~1.05,P>0.05)。结论玛巴洛沙韦治疗儿童流感的有效性和安全性良好,还需开展更高质量研究进一步验证。展开更多
目的探讨玛巴洛沙韦片治疗甲型H1N1流行性感冒(流感)的临床效果及安全性,给临床提供有价值的用药参考信息。方法收集2023年1月1日至12月31日在江苏省中医院住院并应用玛巴洛沙韦片治疗甲型H1N1流感患者的病历资料,对玛巴洛沙韦片的不良...目的探讨玛巴洛沙韦片治疗甲型H1N1流行性感冒(流感)的临床效果及安全性,给临床提供有价值的用药参考信息。方法收集2023年1月1日至12月31日在江苏省中医院住院并应用玛巴洛沙韦片治疗甲型H1N1流感患者的病历资料,对玛巴洛沙韦片的不良反应发生情况(不良反应发生时间、临床表现、严重程度、处理措施和患者转归等)进行回顾性分析,并比较不良反应组和无不良反应组患者的临床特征。结果纳入的176例患者中,有19例患者出现22例次药品不良反应(adverse drug reaction,ADR),ADR发生率为10.80%,其中主要表现为消化系统异常,其次是肝功能异常,均未出现严重的ADR。大部分ADR经对症治疗后均能得到缓解,患者转归良好。统计学分析结果显示,ADR与患者性别、年龄及多数基础疾病不相关,但与肺部的基础疾病相比,不良反应组和无不良反应组之间的差异具有统计学意义(P<0.05)。结论使用玛巴洛沙韦片治疗甲型H1N1流感具有良好的安全性,主要ADR为消化系统反应,需特别关注合并肺部基础疾病患者的用药反应,同时建议治疗期间密切关注患者肝功能。展开更多
目的评价玛巴洛沙韦治疗流行性感冒(以下简称“流感”)的有效性、安全性和经济性,以期为医院新药引进和临床用药决策提供循证参考。方法检索PubMed、Embase、Web of Science、Cochrane Library、Epistemonikos、中国生物医学文献数据库...目的评价玛巴洛沙韦治疗流行性感冒(以下简称“流感”)的有效性、安全性和经济性,以期为医院新药引进和临床用药决策提供循证参考。方法检索PubMed、Embase、Web of Science、Cochrane Library、Epistemonikos、中国生物医学文献数据库、中国知网、维普网、万方数据库及卫生技术评估(HTA)相关学术机构官方网站及数据库,经文献筛选、资料提取、质量评价后,对研究结果进行描述性分析。结果共纳入11篇文献,包括6篇系统评价(SR)/Meta分析、5篇经济学研究。与安慰剂相比,玛巴洛沙韦在缩短流感患者症状缓解时间(TTAS)和退热时间(TTRF)、降低治疗后24h和48h病毒滴度相对于基线的变化水平、降低支气管炎发生率等方面差异有统计学意义(P<0.05)。与神经氨酸酶抑制剂(NAIs)相比,玛巴洛沙韦在缩短流感患者TTRF,降低流感并发症、肺炎、支气管炎发生率等方面差异无统计学意义(P>0.05);多数研究认为玛巴洛沙韦在缩短TTAS方面差异无统计学意义(P>0.05);仅有极低质量文献认为玛巴洛沙韦可显著降低患者治疗后24 h和48 h病毒滴度相对于基线的变化水平。安全性方面,玛巴洛沙韦与帕拉米韦、扎那米韦相比,不良事件(AEs)发生率和药物相关不良事件(DRAEs)发生率差异无统计学意义(P>0.05)。部分研究认为玛巴洛沙韦AEs和DRAEs发生率较安慰剂、奥司他韦、拉尼米韦更低。现有经济学研究显示,在中国与奥司他韦相比、在日本与拉尼米韦相比,玛巴洛沙韦均更具有成本-效果优势。结论与安慰剂相比,玛巴洛沙韦治疗流感具有良好的有效性、安全性和经济性。与NAIs(奥司他韦)相比,玛巴洛沙韦在中国有良好的经济学优势,但在安全性和有效性方面尚需开展更多高质量研究。展开更多
Cap-dependent endonuclease(CEN)in the polymerase acidic protein(PA)of influenza A virus(IAV)represents a promising drug target due to its critical role in viral gene transcription.The CEN inhibitor,baloxavir marboxil(...Cap-dependent endonuclease(CEN)in the polymerase acidic protein(PA)of influenza A virus(IAV)represents a promising drug target due to its critical role in viral gene transcription.The CEN inhibitor,baloxavir marboxil(BXM),was approved in Japan and the US in 2018 and several other countries subsequently.Along with the clinical use of BXM,the emergence and spread of IAV variants with reduced susceptibility to BXM have aroused serious concern.Herein,we comprehensively characterized the in vitro and in vivo antiviral activities of ZX-7101A,an analogue of BXM.The active form of prodrug ZX-7101 showed broad-spectrum antiviral potency against various IAV subtypes,including pH1N1,H3N2,H7N9 and H9N2,in MDCK cells,and the 50%effective concentration(EC_(50))was calculated to nanomole level and comparable to that of baloxavir acid(BXA),the active form of BXM.Furthermore,in vivo assays showed that administration of ZX-7101A conferred significant protection against lethal pH1N1 challenge in mice,with reduced viral RNA loads and alleviated pulmonary damage.Importantly,serial passaging of H1N1 virus in MDCK cells under selection pressure of ZX-7101 led to a resistant variant at the 15th passage.Reverse genetic and sequencing analysis demonstrated that a single E18G substitution in the PA subunit contributed to the reduced susceptibility to both ZX-7101 and BXA.Taken together,our results not only characterized a new CEN inhibitor of IAV but also identified a novel amino acid substitution responsible for CEN inhibitor resistance,which provides critical clues for future drug development and drug resistance surveillance.展开更多
基金Ningbo Top Medical and Health Research Program(Grant No.2022020405)Wu Jieping Medical Foundation(Grant No.320.6750.2023-25-3).
文摘This study analyzed case and prescription data of children aged 12 to 18 years diagnosed with influenza A from the outpatient and emergency departments at the Women and Children’s Hospital of Ningbo University during the influenza epidemic period between February and April 2023.Patients were categorized into two groups based on their medication:the Baloxavir Marboxil group(196 cases)and the Oseltamivir group(126 cases).SPSS Statistics 24.0 software was utilized to compare variables between the two groups,including age,sex,weight,first visit department,number of visits,average prescription cost per patient,drug varieties used,hospitalization rate,and the combined medication usage,to evaluate the relative advantages and disadvantages of the two treatments.The results indicated that the number of visits in the Baloxavir Marboxil group was significantly lower than in the Oseltamivir group,whereas the average prescription cost per patient was higher(P<0.05).There were no significant differences between the two groups regarding age,sex,weight,first visit department,number of drug types used,hospitalization rate,or combined medication usage(P>0.05).When comparing the use of single-class combined drugs,only the quantity of antiviral drugs differed significantly(P<0.05).The Oseltamivir group required more adjuvant treatment with both Chinese and Western antiviral medications.The distribution of the number of combined drug types was concentrated around three and two types in both groups(Baloxavir Marboxil group:41.34%and 39.66%;Oseltamivir group:44.54%and 36.97%).This study highlighted that the new drug,Baloxavir Marboxil,offered certain therapeutic benefits over Oseltamivir in treating influenza among children aged 12 to 18 years,including advantages in single-dose administration,oral compliance,and specific treatment outcomes.The higher unit cost associated with Baloxavir Marboxil might be a factor for further consideration.These findings provided a new reference point for the clinical selection of anti-influenza medications.
文摘流行性感冒发病率高,传染性强,且流感并发症的发病率和死亡率最高。2018年10月,美国食品药品管理局(Food and Drug Administration,FDA)加速批准新型的帽依赖性核酸内切酶抑制剂baloxavir marboxil上市,用于治疗12岁及以上有流感症状且不超过48 h的急性单纯型流感患者。临床研究显示,baloxavir marboxil对流感有较好的客观缓解率。本文对其药理作用、临床评价、安全性及用法用量等进行简要概述。
文摘巴洛沙韦玛波西酯(baloxavir marboxil)是近20年来首创的新作用机制的抗流行性感冒(流感)病毒新药,由日本盐野义(Shionogi)制药株式会社首先研制,作用于流感病毒基因组转录所必需的聚合酶酸性蛋白的内切酶,对甲型和乙型流感病毒均有很强的抑制活性。日本厚生省新药审批部门:日本医药品医疗器械综合机构(Pharmaceuticals and Medical Devices Agency,PMDA)于2015年11月给予该公司单剂治疗≥12岁、无并发症的急性流感优先评审待遇,2018年2月予以加速许可,用于治疗甲型和乙型流感,并于2018年2月23日批准上市,商品名为Xofluza~®。2016年2月盐野义制药公司与瑞士罗氏制药公司签署合作协议,授予罗氏公司除日本和中国台湾地区之外的全球开发与经营权,只保留在美国共同开发权。瑞士罗氏制药集团公司属下的基因泰克(Genentech)制药公司于2018年6月26日获得美国食品药品监督管理局(FDA)优先审评资格,并于2018年10月24日获准上市,商品名为Xofluza~®。该文对巴洛沙韦玛波西酯的非临床和临床药理毒理学、临床研究、不良反应、适应证、剂量与用法、用药注意事项及知识产权状态和国内外研究进展等进行介绍。
文摘Baloxavir marboxil is a polymerase acidic(PA)endonuclease inhibitor,which is approved by the U.S Food and Drug Administration(FDA)on October 25,2018,for the treatment of uncomplicated influenza patients aged 12 years and older.In the present work,we reviewed the pharmacodynamics,pharmacokinetics,drug interactions,clinical trials and adverse reactions of baloxavir marboxil.
文摘目的系统评价玛巴洛沙韦治疗儿童流行性感冒的有效性和安全性。方法检索PubMed、Embase、Web of Science、Cochrane Library、中国生物医学文献数据库、中国知网、万方和维普等数据库,检索时间为建库至2023年11月15日,选取关于玛巴洛沙韦治疗儿童流感病毒感染的随机对照试验和队列研究,分别采用Cochrane风险偏倚评价工具和纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)进行文献质量评价,采用Rev‐Man 5.3软件进行Meta分析。结果共纳入11篇文献,包括3篇随机对照试验和8篇队列研究。与神经氨酸酶抑制剂(奥司他韦、扎那米韦、帕拉米韦和拉尼米韦)相比,玛巴洛沙韦治疗乙型流感的中位发热持续时间较短(17.0 h vs.48.3 h,P<0.01)。与奥司他韦相比,在甲流和乙流亚组中,玛巴洛沙韦组发热持续时间(甲流:MD=-6.30,95%CI:-10.12~-2.49,P=0.001;乙流:MD=-26.94,95%CI:-47.11~-6.77,P=0.009)、症状持续时间[甲流:MD=-11.13,95%CI:-19.34~-2.93,P=0.008;乙流:(4.9±1.3)d vs.(5.4±2.4)d,P<0.01]均更短;在甲流亚组中,玛巴洛沙韦组的中位病毒清除率(单位:log10拷贝数/d)更高[0.81(0.52,1.12)vs.0.63(0.44,0.93),P=0.007];玛巴洛沙韦组复诊率更低(8.05%vs.24.84%,P<0.001)。与扎那米韦相比,玛巴洛沙韦的中位病毒清除率(单位:log10拷贝数/d)差异无统计学意义[甲流:0.81(0.52,1.12)vs.0.90(0.65,1.08),P>0.05;乙流:0.77(0.38,1.04)vs.0.55(0.27,0.77),P>0.05]。与拉尼米韦相比,玛巴洛沙韦的中位病毒清除率(单位:log10拷贝数/d)[甲流:0.81(0.52,1.12)vs.0.76(0.45,1.06),P>0.05;乙流:0.77(0.38,1.04)vs.0.37(0.29,0.56),P>0.05]、复诊率差异无统计学意义(8.05%vs.12.35%,P=0.79)。在安全性方面,玛巴洛沙韦与奥司他韦相比,药物相关不良事件发生率更低(OR=0.66,95%CI:0.44~0.98,P<0.05),总不良事件发生率差异无统计学意义(OR=0.85,95%CI:0.69~1.05,P>0.05)。结论玛巴洛沙韦治疗儿童流感的有效性和安全性良好,还需开展更高质量研究进一步验证。
文摘目的探讨玛巴洛沙韦片治疗甲型H1N1流行性感冒(流感)的临床效果及安全性,给临床提供有价值的用药参考信息。方法收集2023年1月1日至12月31日在江苏省中医院住院并应用玛巴洛沙韦片治疗甲型H1N1流感患者的病历资料,对玛巴洛沙韦片的不良反应发生情况(不良反应发生时间、临床表现、严重程度、处理措施和患者转归等)进行回顾性分析,并比较不良反应组和无不良反应组患者的临床特征。结果纳入的176例患者中,有19例患者出现22例次药品不良反应(adverse drug reaction,ADR),ADR发生率为10.80%,其中主要表现为消化系统异常,其次是肝功能异常,均未出现严重的ADR。大部分ADR经对症治疗后均能得到缓解,患者转归良好。统计学分析结果显示,ADR与患者性别、年龄及多数基础疾病不相关,但与肺部的基础疾病相比,不良反应组和无不良反应组之间的差异具有统计学意义(P<0.05)。结论使用玛巴洛沙韦片治疗甲型H1N1流感具有良好的安全性,主要ADR为消化系统反应,需特别关注合并肺部基础疾病患者的用药反应,同时建议治疗期间密切关注患者肝功能。
基金supported by the National Science and Technology Major Project (2018ZX097110003-005-002)the Key-Area Research and Development Program of Guangdong Province (2022B1111020002)+3 种基金the National Natural Science Foundation of China (NSFC) (32170159,and 82174055)supported by the National Science Fund for Distinguished Young Scholars (81925025)the Innovative Research Group (81621005)of the NSFCthe Innovation Fund for Medical Sciences (2019-I2M-5-049)of the Chinese Academy of Medical Sciences.
文摘Cap-dependent endonuclease(CEN)in the polymerase acidic protein(PA)of influenza A virus(IAV)represents a promising drug target due to its critical role in viral gene transcription.The CEN inhibitor,baloxavir marboxil(BXM),was approved in Japan and the US in 2018 and several other countries subsequently.Along with the clinical use of BXM,the emergence and spread of IAV variants with reduced susceptibility to BXM have aroused serious concern.Herein,we comprehensively characterized the in vitro and in vivo antiviral activities of ZX-7101A,an analogue of BXM.The active form of prodrug ZX-7101 showed broad-spectrum antiviral potency against various IAV subtypes,including pH1N1,H3N2,H7N9 and H9N2,in MDCK cells,and the 50%effective concentration(EC_(50))was calculated to nanomole level and comparable to that of baloxavir acid(BXA),the active form of BXM.Furthermore,in vivo assays showed that administration of ZX-7101A conferred significant protection against lethal pH1N1 challenge in mice,with reduced viral RNA loads and alleviated pulmonary damage.Importantly,serial passaging of H1N1 virus in MDCK cells under selection pressure of ZX-7101 led to a resistant variant at the 15th passage.Reverse genetic and sequencing analysis demonstrated that a single E18G substitution in the PA subunit contributed to the reduced susceptibility to both ZX-7101 and BXA.Taken together,our results not only characterized a new CEN inhibitor of IAV but also identified a novel amino acid substitution responsible for CEN inhibitor resistance,which provides critical clues for future drug development and drug resistance surveillance.
