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FDA新批准的抗HIV药物简介卢洪洲张云智复旦大学医学院附属华山医院传染病科上海 200040随着HIV感染者与艾滋病（AIDS）患者数量的增多，人们对抗HIV药物的研究逐渐深入，不断有新的抗HIV药物出现，为早日攻克艾滋病带来了希望。
但是目前临床所使用的抗艾滋病病毒药物还有很多缺陷，例如无法彻底清除患者体内的病毒、诱导耐药病毒株的出现、产生多种副作用等等。
因此研制出对HIV更有效同时对副作用小的药物是抗艾滋病病毒研制的目标。
1 近两年来FDA新批准的抗HIV的新药主要包括有：①Emtriva(emtricitabine,FTC)：该药物是FDA于02-JUL-03批准的（生产厂家Gilead sciences）抗艾滋病病毒新药。
该药物通过临床实验证实通过抑制逆转录酶的活性降低患者体内艾滋病病毒的负荷，同时可以提高患者体内T细胞的含量，但是该药物无法彻底清除患者体内的艾滋病病毒，通过这两种途径改善了艾滋病患者的疾病、减少继发于HIV感染的疾病发生的危险性。
药物适用于18岁以上的患者，以及已确诊的儿童患者，也适用于抗逆转录病毒药物耐药的患者。
与其它抗艾滋病病毒药物联合使用效果更明显。
剂型为胶囊，用法口服成人200mg，儿童口服液10mg/mL，均每日一次。
副作用包括：头痛、腹泻、恶心呕吐、皮疹、乳酸酸中毒、肝脏肿大、肝脏脂肪堆积、肝中毒、导致HBV继发性感染。
[1]②奈非那韦(nelfinavir mesylate，NFV): Pfizer INC于Jun-1-04出售剂量为625mg/片的NFV，通过药物剂量的加大降低了患者的药物负担，提高疗效，但较250mg/片的NFV其引起腹泻更严重。
③Lexiva(Fosamprenavir Calcium,GW433908,908): 该药物是FDA于20-Oct-03批准的（生产厂家GlaxoSmithKline）抗艾滋病病毒新药，是在amprenavir基础上经进一步研制的抗蛋白酶类的HIV抑制性药物。
• 324 .江苏预防医学 2021 年 5 月第32 卷第3 期Jiangsu J Prev M ed,M ay,2021，Vol. 32,No. 3•疾病防治•替诺福韦联合拉米夫定和依非韦伦治疗HIV/AIDS患者疗效及影响因素张林1，王永素1，牛卫理1，苗瑞红1，张红旗1，陈宝军1，陈俊生21.鹤壁市传染病医院，河南鹤壁458000;2.鹤壁市疾病预防控制中心摘要：目的了解替诺福韦(T D F)+拉米夫定(3T C)+依非韦伦(E F V)方案对H IV/A1D S患者2周的病毒学疗效及影响因素。
方法2018年1月至2019年4月，采用T D F+3T C+E F V方案进行高效抗反转录病毒治疗（H A A R T),且治疗前基线H IV R N A>60c o p y/m l的47例患者为研究对象，采用回顾性研究方法，分析H A A R T治疗2周病毒学疗效及影响因素。
结果47 例H IV/A ID S，临床I 期13 例(27. 66%), II 期8 例（17. 02%), ID期7 例（14_ 89%)，W 期19 例(40. 43%);确诊与开始H A A R T治疗间隔时间0. 87(0. 47,2. 47)个月；治疗前基线C D4细胞计数（279. 62士 183.13)/m m3，C D8细胞计数(895. 70±537.87)/m m3;基线H IV RNA为66 467.07(34 580.00,146 706. 59)co p y/m l。
H A A R T治疗 2 周后，病毒学抑制者31例,病毒抑制率为65. 96%,16例病毒未抑制者2周内HIV R N A每天下降速度为4. 02(3. 51,4. 58)lg(copy/m l)。
多因素lo g istic回归分析结果显示，基线H IV R N A高负荷组治疗2周内H1V抑制是低负荷组的11. 5%，0尺值(95%C J)为0.115 (0.029〜0.465，尸=0.002)。
心血管病学进展２０２４年２月第４５卷第２期 ＡｄｖＣａｒｄｉｏｖａｓｃＤｉｓ，Ｆｅｂｒｕａｒｙ２０２４，Ｖｏｌ．４５，Ｎｏ．２·论著·抑制泛素特异性蛋白酶７改善血管紧张素Ⅱ诱导的心肌细胞肥大陈梦雅 谢赛阳 邓伟（武汉大学人民医院心血管内科代谢与相关慢病湖北省重点实验室，湖北武汉４３００６０）【摘要】目的 探究泛素特异性蛋白酶７（ＵＳＰ７）抑制剂ＦＴ６７１在血管紧张素Ⅱ（ＡｎｇⅡ）诱导的Ｈ９ｃ２细胞肥大中的作用和潜在机制。
方法 将Ｈ９ｃ２细胞随机分为四组：对照组、ＦＴ６７１组、ＡｎｇⅡ组、ＦＴ６７１＋ＡｎｇⅡ组。
利用α ａｃｔｉｎｉｎ细胞免疫荧光染色检测心肌细胞表面积；Ｗｅｓｔｅｒｎｂｌｏｔ检测心房钠尿肽（ＡＮＰ）、脑钠肽（ＢＮＰ）、Ｂ细胞淋巴瘤 ２（Ｂｃｌ ２）、Ｂ细胞淋巴瘤 ２相关Ｘ蛋白（Ｂａｘ）、白细胞介素 ６（ＩＬ ６）、单核细胞趋化蛋白 １（ＭＣＰ １）、肿瘤坏死因子 α（ＴＮＦ α）、ＮＯＤ样受体热蛋白结构域相关蛋白３（ＮＬＲＰ３）以及ＮＡＤＰＨ氧化酶４（Ｎｏｘ４）的蛋白表达水平；ＲＴ ＰＣＲ检测ＡＮＰ、ＢＮＰ、β 肌球蛋白重链（β ＭＨＣ）、ＩＬ ６、ＭＣＰ １、ＴＮＦ α的ｍＲＮＡ表达；ＴＵＮＥＬ染色检测细胞凋亡情况；细胞计数试剂８（ＣＣＫ８）实验检测各组细胞活力；活性氧（ＲＯＳ）染色检测细胞内氧化损伤水平。
结果 与对照组相比，ＡｎｇⅡ组ＵＳＰ７蛋白表达明显增加，而使用ＦＴ６７１后，ＵＳＰ７表达明显被抑制。
与ＡｎｇⅡ组相比，ＦＴ６７１＋ＡｎｇⅡ组心肌细胞面积减小；ＡＮＰ、ＢＮＰ、Ｂａｘ的蛋白表达减少，ＡＮＰ、ＢＮＰ、β ＭＨＣ、Ｂａｘ、ＩＬ ６、ＭＣＰ １以及ＴＮＦ α的ｍＲＮＡ表达减少；Ｂｃｌ ２的蛋白和ｍＲＮＡ表达均增加。
与ＡｎｇⅡ组相比，ＦＴ６７１＋ＡｎｇⅡ组ＴＵＮＥＬ阳性细胞明显减少，心肌细胞活力增强，ＲＯＳ生成减少，Ｎｏｘ４、ＮＬＲＰ３蛋白表达减少，差异具有统计学意义（Ｐ＜０．０５）。
抗艾滋病药物的研究进展毕毅徐进宜吴晓明(中国药科大学药物化学教研室，南京 210009)E-mail: jinyixu @中文摘要本文对已经上市和正在进行临床及临床前研究的抗艾滋病药物进行了综述，其中包括传统的蛋白酶抑制剂，逆转录酶抑制剂，最新发展的融合抑制剂以及具有抗HIV活性的天然化合物等。
关键词艾滋病，抗人类免疫缺陷病毒，蛋白酶抑制剂，逆转录酶抑制剂，融合抑制剂1981年，人类首次发现由人类免疫缺陷病毒（HIV）引起的艾滋病，自此艾滋病在全球迅速蔓延，严重威胁人类的健康和生命安全。
HIV主要有HIV-1和HIV-2两种亚型，其中HIV-1危害性最大，全世界HIV感染者和AIDS患者人数不断增加，我国HIV感染者每年以30%的速度增长，若不加以控制，2010年HIV感染人数将可能达到1000万。
1987年，第一个抗艾滋病药物齐多夫定上市以来，抗艾滋病药物有了突飞猛进的发展。
传统的抗艾滋病药物以病毒复制过程中的蛋白酶和逆转录酶为靶点，进入二十一世纪以来，研究人员的视线转移到很多新的靶点上来，如反义核苷酸药物，融合抑制剂，各类编码基因拮抗剂，新受体合成阻断剂等，部分化合物及肽类化合物已进入临床前及临床阶段研究，与传统的抗艾滋病毒药物相比，具有药效明显，专一性强，毒副作用低等优点。
新靶点药物，复方制剂药物和天然化合物是将来发展抗HIV药物的重要方向。
(1)-(3) 本文将对2000年以来国外批准上市的新药以及正在研究中的前景较好的药物进行综述：1 国外批准上市的药物（3）-（13）2000年至今，有7个新药首次批准进入临床使用，目前抗HIV药物研究发展迅速。
1.1Lopinavir(1) & nitonavir(2)(Kaletra)由雅培公司开发的Kaletra是HIV蛋白酶抑制剂的复方制剂，于2000年9月由FDA批准与逆转录酶抑制剂药物联合用于治疗HIV感染，本复方制剂有胶囊和口服液两种剂型，胶囊每粒含lopinavir133mg&ritonavir33mg,口服液每毫升含lopinavir80mg&ritonavir20mg。
P d D Sh Product Name:Fosamprenavir Calcium Salt CAS No.:226700-81-8Cat. No.:HY-17431Product Data SheetMWt:623.67Formula:C25H34CaN3O9PS Purity :>98%Solubility:DMSOMechanisms:Biological Activity:GW433908 is a phosphate ester prodrug of the antiretroviral protease inhibitor amprenavir, withPathways:Metabolism/Protease; Target:HIV ProteasePathways:Anti-infection; Target:HIV p p p g p p improved solubility over the parent molecule and a potential for reduced pill burden on currentdosing regimens; GW433908G is the calcium salt of the prodrug.IC50 Value:Target: HIV Protease in vitro: There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine[1].i i F i it i d i i t d ith th d did t lt l i References:[1]. Gruber VA, Rainey PM, Moody DE, Interactions between buprenorphine and the proteaseinhibitors darunavir-ritonavir and fosamprenavir-ritonavir. Clin Infect Dis. 2012 Feb 1;54(3):414-23.[2]Cao YJ Smith PF Wire MB Pharmacokinetics and pharmacodynamics of methadone in vivo: Fosamprenavir-ritonavir administered with methadone did not alter plasma amprenavir pharmacokinetics compared with historical control data; nor did it alter the unbound R-methadone at 2 and 6 hours after methadone dosing. Pharmacodyn...[2]. Cao YJ, Smith PF, Wire MB, Pharmacokinetics and pharmacodynamics of methadone enantiomers after coadministration with fosamprenavir-ritonavir in opioid-dependent subjects.Pharmacotherapy. 2008 Jul;28(7):863-74.[3]. Falcoz C, Jenkins JM, Bye C, Pharmacokinetics of GW433908, a prodrug of amprenavir, inhealthy male volunteers. J Clin Pharmacol. 2002 Aug;42(8):887-98.Caution: Not fully tested. For research purposes onlyMedchemexpress LLC18 W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Oct.-10-2018Print Date:Oct.-10-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :Fosamprenavir (Calcium Salt)Catalog No. :HY-17431CAS No. :226700-81-81.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:GW 433908G;GW433908G;GW-433908GFormula:C25H34CaN3O9PSMolecular Weight:623.67CAS No. :226700-81-84. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance White to off-white (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
HIV蛋白酶抑制剂Fosamprenavir郑马庆【期刊名称】《药学进展》【年(卷),期】2003(27)2【总页数】2页(P123-124)【作者】郑马庆【作者单位】无【正文语种】中文【中图分类】R512.91【相关文献】1.HIV蛋白酶抑制剂Darunavir的合成研究进展 [J], 庞永毅;李博文;于晓晶2.HIV—蛋白酶抑制剂在抗HIV治疗中的潜在作用 [J], 刘葆钧3.蛋白酶抑制剂Fosamprenavir Calcium的合成 [J], 胡娟;肖元晶;韩峰燕;杨琍苹4.Impact of Switch to Fosamprenavir and Addition ofLovaza<sup>®</sup>for Treatment of Hypertriglyceridemia in HIV-Infected Subjects on Antiretroviral Therapy [J], Franco Felizarta;Anthony Scarsella;Homayoon Khanlou;Winston Young;Lisa Ross;Henry Zhao;Keith Pappa;Belinda Ha5.Virologic and Lipoprotein Changes after Halving Ritonavir Boosting in HIV-Infected Patients Stabilized on Once-Daily Fosamprenavir plus Abacavir/Lamivudine [J], Dushyantha T. Jayaweera;Gary E. Pakes因版权原因，仅展示原文概要，查看原文内容请购买。
