国产与进口替诺福韦酯治疗慢性乙型肝炎的成本-效果分析

目的:评价国产和进口替诺福韦酯方案治疗慢性乙型肝炎的成本-效果.方法:筛选2018年2月至2019年12月期间就诊于中南大学湘雅医院门诊的慢性乙型肝炎患者,回顾性分析国产和进口替诺福韦酯在乙型肝炎e抗原阳性和阴性患者中应用1年的疗效,根据药物经济学方法进行成本-效果分析及敏感性分析.结果:符合入组标准的患者共计115例...     

替诺福韦酯与恩替卡韦治疗HBeAg阳性慢性乙型肝炎对比研究

目的探究替诺福韦酯与恩替卡韦治疗HBe Ag阳性慢性乙型肝炎(CHB)的效果。方法从本院2012年3月至2013年6月收治的HBe Ag阳性CHB患者80例,按照随机数表法随机抽取组成替诺福韦酯组和恩替卡韦组,每组40例。替诺福韦酯组给予300 mg·d-1替诺福韦酯治疗,恩替卡韦组采用0.5 mg·d-1恩替卡韦治疗。对2组患者治疗前的年龄、性别、HBV DNA定量和ALT水平进行检测比较;对2组患者治疗24周和48周后的ALT复转、HBe Ag阴转和HBV DNA阴转水平进行检测比较;对2组患者治疗48周后的HBV DNA高度应答率进行统计比较。结果治疗24周和48周后,替诺福韦酯组HBe Ag阴转水平均高于恩替卡韦组(P<0.05),HBV DNA阴转和ALT复常水平相似,差异无统计学意义(P>0.05);2组患者的HBV DNA高度应答率差异无统计学意义(P>0.05)。结论替诺福韦酯与恩替卡韦在治疗HBe Ag阳性CHB患者时,替诺福韦酯在患者HBe Ag阴转方面作用显著,安全性较高。     

富马酸丙酚替诺福韦片一种治疗慢性乙肝新药

由美国吉利德科学公司(Gilead sciences)研制的富马酸丙酚替诺福韦片(tenofovir alafenamide tablets,TAF,商品名:Vemlidy),是一种新的核苷(酸)类似物抗病毒药物。临床试验证实,TAF的抗病毒作用高于替诺福韦二吡呋酯(TDF),仅用1/10剂量即可达到与TDF同等药效,同时TAF安全性更高,几乎无肾毒性,骨骼安全性也更高。本文重点对TAF的基本信息、研发动态、临床应用等内容进行介绍。     

富马酸丙酚替诺福韦对阿德福韦酯经治肾功能损伤慢乙肝患者疗效及肾功能影响观察

摘要：目的:观察富马酸丙酚替诺福韦（TAF）对阿德福韦酯（ADV）经治慢性乙型肝炎（CHB）患者的抗病毒疗效及对肾功能的影响作用。方法:服用ADV治疗并出现轻度肾功能异常的CHB患者38例,换用TAF片(25 mg·d-1)抗病毒治疗,观察调整后的抗病毒疗效及患者肾功能指标变化。结果:调整前、调整治疗后24周及48周,所有患者的ALT水平均在正常范围内,未出现肝生化指标异常;HBV DNA均低于检测下限,未出现病毒反弹。调整治疗24周及48周,患者的SCr水平下降,肾小球滤过率（eGFR）升高,与调整前比较差异均有统计学意义（P＜0.05）。结论:TAF可维持ADV经治出现轻度肾功能异常CHB患者的抗病毒效果,且换用后SCr水平及eGFR均有所改善。     

丙酚替诺福韦联合吗替麦考酚酯治疗乙型肝炎相关性免疫球蛋白A肾病的疗效分析

目的 探讨丙酚替诺福韦联合吗替麦考酚酯治疗乙型肝炎相关性免疫球蛋白(immunoglobulin,Ig)A肾病疗效。方法 纳入2016年2月至2020年2月我院收治的乙型肝炎相关性IgA肾病患者共计82例,对其进行病历资料回顾性分析,将采用丙酚替诺福韦治疗的41例患者设为对照组,丙酚替诺福韦联合吗替麦考酚酯治疗的41例患者设为研究组。比较两组临床疗效,对比分析治疗前后两组肝肾功能及乙型肝炎病毒(hepatitis B virus,HBV)血清标志物水平。结果 研究组总有效率为95.12%,显著高于对照组78.05%(P<0.05)。治疗后,两组24 h尿蛋白定量(24-hour urinary protein quantification,24-UCFP)、谷丙转氨酶(alanine aminotransferase,ALT)均显著低于治疗前(P<0.05),白蛋白(albumin,Alb)显著高于治疗前(P<     

阿德福韦酯治疗HBeAg阴性慢性乙型肝炎的成本-效果分析

目的:对阿德福韦酯(贺维力和代丁TM)治疗HBeAg阴性慢性乙型肝炎(CHB)进行成本-效果分析。方法:选取在本院就诊ALT>40IU.L-1的CHB患者136例,分别使用贺维力(66例)和代丁(70例)治疗。疗程48周以上,以HBV-DNA作为抗病毒疗效观察指标,ALT及临床症状改善作为疗效观察指标,以药物成本-效果比作为药物经济学指标。结果:贺维力和代丁两组疗效差异无显著性;增量成本-效果比(△C/△E),代丁有优势。结论:代丁有药物经济学推广价值。     

替诺福韦酯治疗慢性乙型肝炎的研究进展

替诺福韦酯是新型核苷酸类似物,已有临床研究显示,本品对合并感染人免疫缺陷病毒(HIV)及乙型肝炎病毒(HBV)的患者具有较好的疗效,其对拉米夫定耐药者也有良好的抗HBV作用。本文简要综述其药效学、药动学及临床应用。     

替诺福韦酯治疗慢性乙型肝炎的进展

介绍了替诺福韦酯的药理作用及药动学,临床应用,及长期治疗的安全性,从而为临床上治疗乙型肝炎提供更多的用药指导.     

富马酸替诺福韦双特戊酯有关物质的鉴定

目的:采用色谱-质谱联用技术对富马酸替诺福韦双特戊酯中有关物质进行结构鉴定。方法:采用BDS Hypersil C18(250 mm×4.6 mm,5μm)色谱柱,流动相为乙腈-0.2%醋酸铵溶液,梯度洗脱,对富马酸替诺福韦双特戊酯有关物质进行分离;LC-PDA测定各有关物质的UV吸收,甲醇辅助电喷雾正离子化LC-TOF和LC-MS/MS分别测定各有关物质的精密质量和二级质谱。结果:检测到富马酸替诺福韦双特戊酯中存在多个有关物质,其中仅3个的含量在0.1%以上,并鉴定出4个主要有关物质的结构。结论:色谱-质谱联用技术能够有效地鉴定药物中的有关物质,富马酸替诺福韦双特戊酯有关物质鉴定结果对其质量控制和工艺优化提供了参考依据。     

恩替卡韦与阿德福韦酯对慢性乙型肝炎的成本-效果分析

目的 分析恩替卡韦与阿德福韦酯对慢性乙型肝炎的成本-效果。方法 将84例慢性乙型肝炎患者随机分为恩替卡韦组40例和阿德福韦酯组44例治疗,两组均治疗观察12个月。运用药物经济学方法分析其成本-效果（C/E）。结果 治疗3个月恩替卡韦组丙氨酸氨基转移酶（ALT）复常率明显高于阿德福韦酯组,差异有统计学意义（P<0.05）;治疗6、12个月两组ALT复常率无明显差异。治疗3、6、12个月恩替卡韦组乙型肝炎病毒（HBV）-DNA转阴率均明显高于阿德福韦酯组,差异有统计学意义（P<0.05）。治疗3、6、12个月恩替卡韦组乙型肝炎E抗原（HBeAg）转阴率均明显高于阿德福韦酯组,差异有统计学意义（P<0.05）。治疗12个月恩替卡韦组的ALT复常率、HBV-DNA转阴率、HBeAg转阴率的C/E分别为273.3、352.6、911.0,阿德福韦酯组分别为194.2、328.6、908.6。将阿德福韦酯组作为参照,恩替卡韦组HBV-DNA转阴率及HBeAg转阴率的增量成本-效果（△C/△E）分别为129.7、182.1。结论 从短期看,阿德福韦酯治疗慢性乙型肝炎的疗效尚可,药物经济学价值较高,而恩替卡韦虽然疗效更好,但疗效与成本尚未达到理想的平衡。     

Emtricitabine + tenofovir alafenamide for the treatment of HIV

Introduction: Tenofovir alafenamide is a new oral prodrug of tenofovir resulting in relatively low plasma levels and rapid uptake into peripheral blood mononuclear cells in its active form. The United States Food and Drug Administration has now approved this drug coformulated with elvitegravir/cobicistat/emtricitabine, rilpivirine/emtricitabine and emtricitabine. United States guidelines now list this formulation as one of the preferred components of a variety of antiretroviral regimens, and is included as an alternative in other international guidelines, with the notable exception of the World Health Organization, mostly due to limited availability.

Areas covered: This review covers pre-clinical and clinical data searched through PubMed? up to August 2016.

Expert opinion: Tenofovir alafenamide is effective as part of an antiretroviral regimen. There is also compelling data that it has less adverse effects on bone mineral density and possibly kidneys than tenofovir disoproxil fumarate. Although approved for use in those with estimated glomerular filtration rates as low as 30 mL/min, data is somewhat limited in this group. While there are few reasons to not use tenofovir alafenamide as a substitute for tenofovir disoproxil fumarate, the former should not be used with rifamycins, is not yet recommended in pregnancy and needs to be studied further before it can be considered as part of a pre-exposure prophylaxis regimen.     

Tenofovir and emtricitabine concentrations in hair are comparable between individuals on tenofovir disoproxil fumarate versus tenofovir alafenamide-based ART

Tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) is the backbone for both human immunodeficiency virus (HIV) treatment and pre-exposure prophylaxis (PrEP) worldwide. Tenofovir alafenamide (TAF) with FTC is increasingly used in HIV treatment and was recently approved for PrEP among men-who-have-sex-with-men. TDF and TAF are both metabolized into tenofovir (TFV). Antiretrovirals in plasma are taken up into hair over time, with hair levels providing a long-term measure of adherence. Here, we report a simple, robust, highly sensitive, and validated high-performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS)-based analytical method for analyzing TFV and FTC from individuals on either TDF/FTC or TAF/FTC in small hair samples. TFV/FTC are extracted from ~5 mg hair and separated on a column using a gradient elution. The lower quantification limits are 0.00200 (TFV) and 0.0200 (FTC) ng/mg hair; the assay is linear up to 0.400 (TFV) and 4.00 (FTC) ng/mg hair. The intra-day and inter-day coefficients of variance (CVs) are 5.39–12.6% and 6.40–13.5% for TFV and 0.571–2.45% and 2.45–5.16% for FTC. TFV concentrations from participants on TDF/FTC-based regimens with undetectable plasma HIV RNA were 0.0525 ± 0.0295 ng/mg, whereas those from individuals on TAF/FTC-based regimens were 0.0426 ± 0.0246 ng/mg. Despite the dose of TFV in TDF being 10 times that of TAF, hair concentrations of TFV were not significantly different for those on TDF versus TAF regimens. Pharmacological enhancers (ritonavir and cobicistat) did not boost TFV concentrations in hair. In summary, we developed and validated a sensitive analytical method to analyze TFV and FTC in hair and found that hair concentrations of TFV were essentially equivalent among those on TDF and TAF.     

Elvitegravir,cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults

Introduction: Tenofovir alafenamide (TAF) is is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations as compared to tenofovir disoproxil fumarate (TDF) and such property suggests that TAF-containing regimens can improve renal and bone safety compared with TDF-containing regimens. Single tablet regimen elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF) is the first coformulation that includes TAF in place of TDF. This review aims to provide an overview of its role in the treatment of HIV infection.

Areas covered: This review covers pre-clinical and clinical data serached through Medline and Pubmed up to August 2015.

Expert opinion: In terms of efficacy, E/C/F/TAF was found to be non inferior to E/C/F/TDF in naive patients, and more effective in patients switching from TDF-based regimens with efavirenz or boosted PI. In safety analyses, E/C/F/TAF was constantly found to be associated with significant improvement of renal function and urinary markers of proximal tubulopathy, and significant improvement of bone mineral density (BMD) as compared to TDF-containing regimens. E/C/F/TAF, as a new single tablet regimen, appeared to be promising for optimization of cART tolerability in HIV-infected patients.     

富马酸丙酚替诺福韦片健康人体生物等效性评价

目的评价富马酸丙酚替诺福韦片受试制剂及参比制剂在健康人体的生物等效性与安全性。方法选取符合纳入标准的参与空腹试验受试者43例与餐后试验受试者49例。依照单中心、随机、开放、单剂量空腹/餐后给药、双周期/三周期交叉试验方案,口服富马酸丙酚替诺福韦片受试制剂及参比制剂。采用液相色谱—串联质谱法测定服药后48 h内22个不同时间点的血药浓度,计算主要药动学参数。采用方差分析,双单侧t检验和90%置信区间分析进行生物等效性评价并统计不良事件发生率以进行安全性评价。结果受试制剂与参比制剂的药动学评价指标(AUC和Cmax)具有生物等效性,且安全性均较好。结论富马酸丙酚替诺福韦片受试制剂与参比制剂吸收的速度与程度基本一致,在空腹和餐后给药条件下生物等效性和安全性均良好。     

HS-GC-MS/MS测定富马酸丙酚替诺福韦中微量的基因毒性杂质N-亚硝基二甲胺

目的 采用顶空进样气相色谱三重四级杆质谱联用（HS-GC-MS/MS）法测定富马酸丙酚替诺福韦中微量的基因毒性杂质N-亚硝基二甲胺（NDMA）。方法 采用三重四极杆GC-MS/MS,Agilent VF-WAX ms（30 m×0.25 mm,1 μm）色谱柱,载气：氦气;恒流模式1.0 mL·min^-1;程序升温,进样口温度230℃,顶空温度130℃;质谱采用电子轰击电离源（EI）,电离能量为70 eV,离子源温度230℃,多反应监测（MRM）模式进行检测,溶剂为N-甲基吡咯烷酮（NMP）。进行专属性、系统适用性、检测限与定量限、线性与范围、准确度、精密度、溶液稳定性、耐用性考察。结果 NDMA与相邻色谱峰之间分离效果良好;NDMA在7.0～105.0 ng·mL^-1线性关系良好,检测限为3.5 ng·mL^-1,定量限为7.0 ng·mL^-1;NDMA低、中、高质量浓度（56、70、84 ng·mL^-1）回收率为95.6%～109.3%,RSD为4.0%（n=9）;重复性试验NDMA质量浓度RSD为6.5%,中间精密度RSD为6.1%;对照品溶液室温放置24 h稳定,供试品溶液室温放置90 h内溶液稳定;保持其他条件不变,分别改变进样口温度（230、225、235℃）、离子源温度（230、225、235℃）、载气体积流量（1.0、0.9、1.1 mL·min^-1）、顶空温度（130、128、132℃）,方法耐用性良好。结论 所建立的方法准确度好、灵敏度高、简便可靠,对仪器污染小,可用于富马酸丙酚替诺福韦中NDMA的质量控制。     

Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection

Introduction: In April 2017 tenofovir alafenamide (TAF) was added to the list of first-line therapies recommended for chronic hepatitis B (CHB). TAF has pharmacology similar to tenofovir disoproxil fumarate (TDF) with higher cell delivery to the hepatocytes but less systemic exposure.

Areas covered: We review here studies leading to TAF’s approval and comparing it to TDF. In two major clinical trials, TAF was non-inferior to TDF in achieving HBV DNA levels below 29 IU/ml. TAF-treated patients had significantly smaller decreases in bone mineral density (BMD) at the hip and spine in both HBeAg-positive and HBeAg-negative patients, and smaller mean increases in serum creatinine, although the difference was only statistically significant in HBeAg-positive patients. Patients treated with TDF for 96 weeks and then switched to TAF had improvements in renal and BMD measures only 24 weeks after switching.

Expert commentary: With clear evidence from major studies showing that TAF is safe, tolerable, and non-inferior to TDF, its recommendation as a first-line therapy is appropriate. Longer term follow up will be required to determine if the differences in adverse bone and kidney effects seen with TAF in comparison to TDF will be clinically relevant.