Adaptation of Blood-stage Controlled Human Malaria Infection for Evaluation of Transmission Blocking Malaria Interventions in Malaria Endemic Countries

Controlled human malaria infection (CHMI) has revolutionized the development of malaria vaccines. It involves the administration of either known numbers of sporozoites or infected erythrocytes to healthy human volunteers under a controlled environment. The use of highly sensitive molecular malaria diagnostic methods informs treatment decisions before symptom development and allows the characterization of parasite growth dynamics. Sporozoite CHMI has safely been used in six countries in Africa providing a platform to assess the efficacy of candidate malaria vaccines and study the natural immunity to malaria. Blood stage CHMI involves administration of known number of Artemether Lumefantrine sensitive infected erythrocytes in healthy volunteers, and it is a more sensitive model for modelling parasite growths and study the efficacy of blood-stage malaria vaccines. It has been safely used in Australia and Europe but not in Africa. Adaptation of this model by administration of combination of suboptimal and optimal antimalarial drugs lead to increased gametocytaemia, and infection rates in mosquitoes following standard membrane feeding assay. Such adaptation allows the model to be used to study parasite transmission from human to mosquitoes and evaluate transmission blocking malaria interventions.
There is an urgent need to establish an in vivo model for early-stage clinical evaluation of transmission blocking interventions (TBI) in volunteers living in malaria endemic countries. This would allow rapid and cost-effective way to down-select transmission blocking candidate malaria vaccine and gametocidal antimalarial drugs before larger, more complex, and expensive field efficacy studies are conducted. A study done in naïve individual showed 100% success in establishing a malaria infection using 2800 P. falciparum infected RBCs, while a recent study (manuscript in development) has demonstrated success in establishing infection in Tanzanian semi-immune individuals with low malaria exposure using 1000 P. falciparum infected RBCs. We will use 1000 ALU-sensitive 3D7 P. falciparum infected RBCs to establish an in vivo transmission model for studying Transmission blocking interventions and assess the efficiency of two antimalarial drugs regimens (Piperaquine and doxycycline) to induce high levels of gametocytaemia and mosquito infection rates in healthy African adults. We will also investigate the determinants of successful transmission to mosquitoes including underlying immune responses to both asexual and sexual malaria antigens, asexual parasite dynamics and gametocyte burden, sex ratio of male and female gametocytes, and the relationship between gametocyte density and mosquito infection rate

开始日期2024-01-09

申办/合作机构

Ifakara Health Institute

[+1]

NCT05930782 / Completed临床1期IIT

A Randomized, Open Label, Two-part, Parallel-group, Phase I Study to Evaluate the Pharmacokinetics of Piperaquine Oral Dispersible Granules Formulation Compared to Piperaquine Hard Tablets Administered as a Single Dose in Fasting Condition (Part 1) and of Piperaquine Oral Dispersible Granules Formulation Administered as Single Dose in Various Fed States (Part 2) in Healthy Adult Participants

This trial aims to characterise the pharmacokinetic (PK) profile and estimate drug exposure of a single oral dose of piperaquine (PQP) in a dispersible granule formulation compared to the PQP hard tablet formulation in the fasted state (Part 1), to advise the selection of dose when the PQP granule formulation is administered in a fed state in healthy adult participants. Part 2 will assess the effect on different types of meal composition on the PK of a single dose of PQP granule formulation in healthy adult participants.

开始日期2023-07-24

申办/合作机构

MMV Medicines for Malaria Venture

ACTRN12623000239662 / Not yet recruiting临床4期

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Alikadam Upazila and Lama Upazila of Bandarban district and Baghaichari Upazila of Rangamati districts, Bangladesh.

开始日期2023-03-07

申办/合作机构

Bangladesh Ministry of Health & Family Welfare

100 项与磷酸哌喹相关的临床结果

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100 项与磷酸哌喹相关的转化医学

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100 项与磷酸哌喹相关的专利（医药）

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844

项与磷酸哌喹相关的文献（医药）

2024-12-31·Journal of pharmaceutical policy and practice

Private sector availability and affordability of under 5 malaria health commodities in selected states in Nigeria and the Federal Capital Territory

Article

作者: Dabes, Chrysantus ; Itiola, Ademola Joshua ; Biambo, Ahmed Aminu ; Aidenagbon, Adaeze ; Iwegbu, Azuka ; Onabajo, Sarah ; Oguoma, Chibuzo ; Oresanya, Olusola ; Fagbemi, Babatunde ; Rotimi, Kunle ; Ibinaiye, Taiwo

Background:

To guarantee uninterrupted service delivery, quality-assured products must be affordable and continuously available across all sectors, including the private sector, which provides more than 60% of healthcare services in Nigeria. We investigated the private sector availability and affordability of under 5 malaria commodities to establish the level of access in this sector.

Methods:

We surveyed patent medicine and pharmacy stores across seven states in Nigeria and the Federal Capital Territory to establish the availability and affordability of selected malaria commodities for children under 5 years. Availability was measured as the percentage of visited outlets with the product of interest on the day of visit, while affordability was assessed by establishing if it cost more than a day's wage for the least-paid government worker to purchase a full course of malaria diagnostic test and/or medication.

Results:

Artemisinin-based antimalarials for uncomplicated and severe malaria were the most available commodities. SPAQ1 and SPAQ2 used for seasonal malaria chemoprevention campaign were surprisingly also available in some outlets. However, only about half (48.3% and 53.3%) of the surveyed outlets had stock of artemether/lumefantrine (AL1) and artesunate injection, respectively. The median price of surveyed products ranged from USD (United States Dollars) 0.38 to USD 2.17 per treatment/test. Except for amodiaquine tablet and artemether injection, which cost less, all other originator brands cost the same or more than the lowest-priced generic. Antimalarial products were affordable as their median prices were not more than a day's wage for the least-paid government worker. However, when the cost of testing and treatment with artemisinin-based combination therapies (ACTs) was assessed, testing and treatment with dihydroartemisinin/piperaquine were unaffordable as the they cost more than 1.5 times the daily wage of the least-paid government worker.

Conclusion:

The overall private sector availability of under-five malaria commodities in surveyed locations was suboptimal. Also, testing and treatment with recommended ACTs were not affordable for all surveyed products. These findings suggest the need for interventions to improve access to affordable under-five malaria commodities.

2024-03-01·European journal of medicinal chemistry

Discovery of new piperaquine hybrid analogs linked by triazolopyrimidine and pyrazolopyrimidine scaffolds with antiplasmodial and transmission blocking activities

Article

作者: Boechat, Nubia ; Nogueira, Fatima ; Aguiar, Anna C C ; Duarte, Denise ; de Souza, Guilherme E ; Morais, Ines ; Guido, Rafael V C ; Maluf, Sarah El Chamy ; Ferreira, Maria de Lourdes G ; Zapata, Luana ; Nonato, M Cristina ; Pinheiro, Luiz C S ; de Souza, Juliana O ; Feitosa, Livia M ; Franca, Rodolfo Rodrigo F

The World Health Organization (WHO) estimated that there were 247 million malaria cases in 2021 worldwide, representing an increase in 2 million cases compared to 2020. The urgent need for the development of new antimalarials is underscored by specific criteria, including the requirement of new modes of action that avoid cross-drug resistance, the ability to provide single-dose cures, and efficacy against both assexual and sexual blood stages. Motivated by the promising results obtained from our research group with [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine derivatives, we selected these molecular scaffolds as the foundation for designing two new series of piperaquine analogs as potential antimalarial candidates. The initial series of hybrids was designed by substituting one quinolinic ring of piperaquine with the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine nucleus. To connect the heterocyclic systems, spacers with 3, 4, or 7 methylene carbons were introduced at the 4 position of the quinoline. In the second series, we used piperazine as a spacer to link the 1,2,4-triazolo[1,5-a]pyrimidine or pyrazolo[1,5-a]pyrimidine group to the quinoline core, effectively merging both pharmacophoric groups via a rigid spacer. Our research efforts yielded promising compounds characterized by low cytotoxicity and selectivity indices exceeding 1570. These compounds displayed potent in vitro inhibitory activity in the low nanomolar range against the erythrocytic form of the parasite, encompassing both susceptible and resistant strains. Notably, these compounds did not show cross-resistance with either chloroquine or established P. falciparum inhibitors. Even though they share a pyrazolo- or triazolo-pyrimidine core, enzymatic inhibition assays revealed that these compounds had minimal inhibitory effects on PfDHODH, indicating a distinct mode of action unrelated to targeting this enzyme. We further assessed the compounds' potential to interfere with gametocyte and ookinete infectivity using mature P. falciparum gametocytes cultured in vitro. Four compounds demonstrated significant gametocyte inhibition ranging from 58 % to 86 %, suggesting potential transmission blocking activity. Finally, we evaluated the druggability of these new compounds using in silico methods, and the results indicated that these analogs had favorable physicochemical and ADME (absorption, distribution, metabolism, and excretion) properties. In summary, our research has successfully identified and characterized new piperaquine analogs based on [1,2,4]triazolo[1,5-a]pyrimidine and pyrazolo[1,5-a]pyrimidine scaffolds and has demonstrated their potential as promising candidates for the development of antimalarial drugs with distinct mechanisms of action, considerable selectivity, and P. falciparum transmission blocking activity.

2024-02-01·The Lancet. Infectious diseases

Effect of primaquine dose on the risk of recurrence in patients with uncomplicated Plasmodium vivax: a systematic review and individual patient data meta-analysis

Review

作者: Awab, Ghulam R ; Longley, Rhea J ; Sutanto, Inge ; Vieira, José Luiz F ; Barber, Bridget E ; Pukrittayakamee, Sasithon ; Baird, J Kevin ; Grigg, Matthew J ; Abreha, Tesfay ; Commons, Robert J ; Gonzalez-Ceron, Lilia ; Ladeia-Andrade, Simone ; White, Nicholas J ; Thanh, Pham V ; Watson, James A ; Simpson, Julie A ; Cui, Liwang ; Pasaribu, Ayodhia P ; Zuluaga-Idarraga, Lina M ; Rijal, Komal R ; Hwang, Jimee ; Rajasekhar, Megha ; Karunajeewa, Harin ; Thriemer, Kamala ; Pereira, Dhelio B ; Lidia, Kartini ; Daher, André ; Llanos-Cuentas, Alejandro ; Price, Ric N ; Guerin, Philippe J ; Lacerda, Marcus V G ; Edler, Peta ; Taylor, Walter R J ; Chu, Cindy S

BACKGROUND:

Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence.

METHODS:

For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5-7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470.

FINDINGS:

Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2-53·9) in 1470 patients treated without primaquine, 19·3% (16·9-21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0-9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17-0·27; p<0·0001) and high-dose primaquine (0·10, 0·08-0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5-7 were reported by 4·0% (95% CI 0·0-8·7) of 893 patients treated without primaquine, 6·2% (0·5-12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8-10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7-16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias.

INTERPRETATION:

Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms.

FUNDING:

Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.

项与磷酸哌喹相关的新闻（医药）

2024-03-02

·生物探索

Nat Commun | 厦门大学李剑课题组发现疟原虫抗药的新机制

引言疟疾是由疟原虫感染引起的传染性寄生虫病，全球每年有超过2.4亿人感染，造成~60万人死亡。当前，恶性疟原虫几乎对所有类型的抗疟药包括青蒿素及青蒿素类复方药均产生了不同程度的抗性。抗药性疟原虫的出现、演化及蔓延是疟疾防治和根除的主要难题。跨膜转运蛋白MDR1是哺乳类P-gp蛋白的同源物，早期的研究显示MDR1定位于疟原虫的消化泡（digestive vacuole, DV）泡膜。该蛋白可转运不同类型的抗疟药/引起不同的药敏反应而受到耐药性研究领域的广泛关注。然而，调控MDR1亚细胞定位及抗药性发生的机制一直是个谜。2024年2月27日，厦门大学生命科学学院李剑课题组在Nature Communications 发表题为“Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance”的研究论文，该研究揭示疟原虫去泛素化酶UBP1突变体通过调节MDR1的泛素化和改变其细胞定位，介导MDR1对多种抗疟药的外排，引起疟原虫产生多重抗药性。研究人员首先通过甲氟喹（mefloquine）筛选、构建遗传杂交和遗传定位，发现约氏疟原虫的UBP1编码基因与抗药表型相连锁，并新发现两个独特的与抗药性相关的点突变I1560N和P2874T（均为疏水性氨基酸突变为亲水性氨基酸），突变位点分别位于CCR和UCH功能结构域。接着研究人员应用基因编辑技术对敏感性虫株（IP单倍型）和抗性虫株（NT单倍型）的ubp1进行一系列单点和双点等位替换，正向及反向替换的药敏测试结果证明在两个位点同时突变的情形下疟原虫具有多重抗药性，即突变体对甲氟喹、苯芴醇（lumefantrine）及哌喹（piperaquine）等抗疟药（常用作青蒿素类复方的伴侣药物）均产生了抗性。深入的表型分析阐明双点突变不仅损坏UBP1去泛素化酶的生理功能，而且显著降低原虫率和消化泡中疟色素的生成。UBP1蛋白含有3100多个氨基酸，分析显示该蛋白序列存在高度的固有无序域（intrinsically disordered region, IDR），提示其可通过相分离形成无膜细胞器或凝聚体。质谱鉴定和免疫印迹研究表明，MDR1是UBP1酶促作用的底物蛋白。机制分析发现，野生型UBP1形成具功能性的点状凝聚体对MDR1进行去泛素化，脱泛素化的MDR1定位于消化泡膜；而突变型UBP1由于IP→NT突变破坏了凝聚体的形成及酶活性，导致MDR1泛素化水平升高，造成MDR1易位至细胞质膜，此时MDR1可将抗疟药泵出胞外以降低胞内的药物浓度，致使疟原虫获得抗性。最后，研究者使用P-gp抑制剂他立喹达（tariquidar）与甲氟喹等进行联合用药，发现组合用药可显著杀灭抗性疟原虫。模式图（Credit: Nature Communications）该研究发现并解析了一种新的疟原虫抗药机制：UBP1位点突变→凝聚体及酶活性受损→泛素化水平升高致使MDR1从消化泡膜易位至细胞质膜→药物外排→抗药性产生。研究结论对于抗药性的监测，抗疟药研发和联合用药有重要的指导意义。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s41467-024-46006-3责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文Nature | 癌症与神经系统的致命舞蹈

2024-01-13

·Science Daily

African women living with HIV have an effective option to prevent malaria during pregnancy

In women living with HIV, preventive treatment with DHA-PPQ is a safe and effective strategy to prevent malaria during pregnancy, according to the final results of the MAMAH clinical trial. In women living with HIV, preventive treatment with DHA-PPQ is a safe and effective strategy to prevent malaria during pregnancy, according to the final results of MAMAH, a clinical trial funded by the European & Developing Countries Clinical Trials Partnership (EDCTP) and coordinated by the Barcelona Institute for Global Health (ISGlobal), an institution supported by "la Caixa" Foundation. The study, published in the Lancet Infectious Diseases, could help protect the health of the estimated one million pregnant women who suffer from a double infection with malaria and HIV every year. Pregnant women are particularly vulnerable to malaria infection. Hence the recommendation to offer preventive treatment (IPTp) based on sulphadoxine and pyrimethamine (SP) to pregnant women living in malaria-endemic areas. The problem is that these drugs are incompatible with co-trimoxazole (CTX), an antibiotic given to people with HIV to prevent bacterial infections. "This means that the population most vulnerable to malaria infection and its consequences, namely pregnant women living with HIV, are also the least protected," explains ISGlobal researcher Raquel González, technical coordinator of the MAMAH project, led by Clara Menéndez, director of ISGlobal's Maternal, Child and Reproductive Health Initiative. The aim of the project was to evaluate the safety and efficacy of two other drugs: dihydroartemisinin and piperaquine (DHA-PPQ) to prevent malaria during pregnancy in women living with HIV. The research team conducted the trial in Gabon and Mozambique with more than 600 pregnant women taking CTX in addition to antiretroviral treatment for HIV. One group of pregnant women received DHA-PPQ and the other group received a placebo. Lower risk of malaria infection and disease Although there was no significant difference in malaria infection at the time of delivery, women in the DHA-PPQ group had a significantly lower risk of developing clinical malaria throughout pregnancy (almost eight times lower than the placebo group) and also a lower risk (almost half) of becoming infected. DHA-PPQ was effective in women taking different antiretroviral treatments. No serious side effects were observed, and DHA-PPQ had no effect on mother-to-child transmission of HIV. "We show that preventive treatment with DHA-PPQ is effective even in low malaria transmission settings," says Gonzalez. "Adding this strategy to malaria control tools could significantly improve the health of thousands of mothers and their babies, especially in sub-Saharan Africa, a region where an estimated one million women living with HIV are infected with malaria during pregnancy every year," she adds. "We congratulate the MAMAH team on these important results in the field of malaria research, and, in particular, in providing better health to pregnant women living with HIV in malaria-endemic areas," says Montserrat Blázquez-Domingo, EDCTP Senior Project Officer. "This study underlines the value of collaborative research that EDCTP supports and our focus on priority infectious disease affecting sub-Saharan Africa in populations often excluded from clinical trials -- such as pregnant women." The MAMAH study is part of the EDCTP2 Programme supported by the European Union (grant number RIA2016MC-1613-MAMAH).

临床结果临床研究

2023-11-19

·蒲公英Ouryao

【出海新进展】3药品分别出口FDA、WHO和以色列

来源：企业公告整理：wangxinglai2004近日，三药企分别发布了产品海外上市进展公告，具体为亿帆生物创新药艾贝格司亭α注射液获得FDA上市批准、普利药业制剂依替巴肽注射液获得以色列上市许可、华润三九下属公司昆药集团抗疟疾药品双氢青蒿素磷酸哌喹片通过WHO预认证。亿帆生物制剂获FDA上市批准一、药物基本情况药品通用名：艾贝格司亭α注射液中文商品名：亿立舒® 英文商品名：Ryzneuta® 申请事项：生物制品许可申请美国获批适应症：RYZNEUTA®是一种白细胞生长因子，用于成年非髓性恶性肿瘤患者在接受容易引起发热性中性粒细胞减少症的骨髓抑制性抗癌药物治疗时，降低以发热性中性粒细胞减少症为表现的感染发生率。二、药物其他相情况 Ryzneuta®是基于控股子公司Evive Biotech Ltd.具有自主知识产权 Di-KineTM双分子技术平台开发的治疗用一类生物制品新药，是基于Fc融合蛋白技术，由CHO细胞表达的rhG-CSF二聚体，具有长效和强效的生物学特点。目前 Ryzneuta®主要应用于预防及治疗肿瘤患者在接受抗癌药物出现嗜中性粒细胞减少症，可使肿瘤化疗患者嗜中性粒细胞迅速增殖和恢复，从而增强了免疫系统抵抗感染的能力，以防止患者在化疗期间死于感染或者其他相关并发症，也使得患者能完成完整的化疗周期，取得更好的抗肿瘤治疗效果。 2018年1月，亿一生物完成了Ryzneuta®首个在美国及欧洲开展的 III 期临床试验（以下简称“04 试验”），并达到预设主要疗效终点，受试者耐受情况良好，安全性达到预期。2020年1月5日，亿一生物收到在中国开展的 Ryzneuta® 的 III 期临床试验《统计数据图表合集》，统计结果表明，Ryzneuta®中国 III 期临床试验的有效性结果已全面达到临床试验预设评价标准，疗效与对照药品（原研进口药品重组人粒细胞集落刺激因子）相当；2020 年 6 月，亿一生物收到在美国及欧洲开展的第二个国际 III 期临床试验（以下简称“05 试验”）《统计数据图表合集》，结果显示，第二个国际 III 期临床试验成功达到预设主要疗效终点和次要疗效终点，药物疗效与对照药品（美国安进公司原研产品Neulasta）相当；2020年7月，公司完成了05试验有关免疫原性的中和抗体检测，结果为阴性，标志着无药物相关的抗体产生；自此，Ryzneuta®国内外开展的 I 期、II 期及 III 期临床试验，均圆满达到临床试验预设目标。2021年3月30日，亿一生物就 Ryzneuta®向FDA提交了 Ryzneuta®的生物制品许可申请，并于2021年5月27日收到 FDA的受理函，正式接受 Ryzneuta®的上市申请。 2021年8月26日，公司、亿一生物与中国生物制药有限公司附属公司正大天晴药业集团股份有限公司及其全资子公司正大天晴药业集团南京顺欣制药有限公司签订了《商业化合作协议》，约定将Ryzneuta®相关的在中国境内的商业化权益独家许可给天晴南京顺欣，天晴南京顺欣需向亿一生物支付最高额不超过21,000万元的许可费，以及分级的净销售额提成费。 2021年9月30日，亿一生物收到欧洲药品管理局（以下简称：“EMA”）签发的关于 Ryzneuta®上市许可申请受理函，并进入审评程序。 2022年2月23日，公司收到国家药品监督管理局签发的 Ryzneuta®境内生产药品注册上市许可申请《受理通知书》。 2022年3月31日，公司收到FDA的邮件通知，因旅行限制FDA将推迟 Ryzneuta®上市申请批复，直到现场检查完成。普利制药制剂获以色列上市许可一、药物基本情况（一）药物名称：依替巴肽注射液（二）适应症：1、用于急性冠状动脉综合征（不稳定型心绞痛/非ST段抬高型心肌梗死）患者，包括接受药物治疗的患者和进行经皮冠状动脉介入术（PCI ）的患者，以降低死亡或新发生心肌梗死的联合终点发生率。2、用于进行经皮冠状动脉介入术（PCI）的患者，包括进行冠状动脉内支架置入术的患者，以降低死亡、新发生心肌梗死或需要紧急介入治疗的联合终点发生率。（三）剂型：注射剂（四）规格：20mg/10mL（2mg/mL）、75mg/100mL（0.75mg/mL）。（五）生产商：海南普利制药股份有限公司二、药物其他相情况依替巴肽是血小板糖蛋白IIb/IIIa受体拮抗剂。通过选择性、可逆性抑制血小板聚集的最终共同通路，可逆转因血栓形成而导致的缺血状态。适用于急性冠状动脉综合症患者的治疗。依替巴肽注射液于1998年5月在美获准上市，现由默克公司负责销售，1999年7月在欧洲获准上市，现由葛兰素史克公司负责销售；商品名均为INTEGRILIN，目前已在全球广泛上市销售。普利制药的依替巴肽注射液成功研发后进行了多国注册申报，已于2018年2 月获得荷兰上市许可，于2018年7月获得德国上市许可，于2019年1月获得美国上市许可，于2019年8月获得英国上市许可，于2021年7月获得国家药品监督管理局颁发的药品注册批件，于2023年3月获得泰国上市许可，于2023年8月获得加拿大上市许可。近日，公司收到以色列卫生部的上市许可，标志着普利制药具备了在以色列销售依替巴肽注射液的资格，将对公司拓展以色列市场带来积极影响。华润三九制剂通过WHO预认证一、药物基本情况药物名称：双氢青蒿素磷酸哌喹片 40mg/320mg Dihydroartemisinin/Piperaquine phosphate Tablet, Film-coated 40mg/320mg持证人:北京华方科泰医药有限公司（昆药集团下属全资子公司）制剂生产厂家:贝克诺顿（浙江）制药有限公司（昆药集团下属全资孙公司）二、药物其他相情况据 WHO《世界疟疾报告2022》统计，全球2021年疟疾感染病例为2.47亿例，疟疾死亡病例为62.5万例。目前，以青蒿素为基础的复方疗法依然是恶性疟疾最有效的治疗方法；2021年，全球通过国际公立市场采购共分发2.42亿份青蒿素类药物。目前，全球有三个双氢青蒿素磷酸哌喹片 40mg/320mg供应商（含昆药集团）通过PQ认证。昆药集团借助青蒿素产品的销售，已形成覆盖50多个国家的国际销售网络；其中双氢青蒿素磷酸哌喹片40mg/320mg在24个国家注册并进行商业市场销售。2022年，该产品销售收入2,366.34万元人民币。WHO的PQ认证是国际组织采购药品的重要门槛。本次昆药集团的抗疟药产品通过 PQ 认证，昆药集团成为国际公立采购市场的合格供应商，为昆药集团扩展国际公立市场提供了有力的支撑和保证；同时，通过本次PQ认证进一步提升了昆药集团质量管理体系及质量文化，为昆药集团其他产品的国际化认证积累了经验，有利于加速昆药集团产品的国际化进程。

上市批准临床3期

100 项与磷酸哌喹相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	磷酸哌喹	P01B	-

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
疟疾	中国	上海上药信谊药厂有限公司	-
疟疾	中国	上海中西三维药业有限公司	-
疟疾	中国	海南全星制药有限公司	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02431637 (CTgov)	临床1期	疟疾	6	Administration of the malaria inoculum+Piperaquine Phosphate 480 mg	蓋鹽鹽積壓範淵鏇衊齋(壓夢簾衊襯積窪觸膚鬱) = 餘觸夢艱憲夢鬱鑰壓襯廠網築糧憲遞繭鹽願壓 (製選襯鏇繭顧艱遞遞遞, 窪積窪淵衊醖網構願齋 ~ 膚艱顧願壓壓艱衊鏇簾) 更多	-	2020-05-26
NCT02198807 (Pubmed \| Clin Infect Dis)	临床2期	恶性疟	100	Fosmidomycin-piperaquineFosmidomycin-piperaquine	遞壓鏇鏇鬱憲鑰廠遞醖(簾鹽遞觸願製廠衊窪衊) = The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity 膚鹹簾憲簾築艱艱壓廠 (構獵選積網夢壓襯選繭 )	-	2018-06-01
NCT01288820 (Pubmed \| Am J Trop Med Hyg)	临床3期	间日疟原虫感染	331	Artesunate-amodiaquine (AAQ) + Primaquine (PQ)	糧鹹襯衊觸齋鹹簾構蓋(鹹網齋艱鹽憲衊艱鹽醖) = 鹽壓積觸夢壓簾窪選簾選積鑰網鬱製窪網遞窪 (製構網鹹鏇艱齋構鏇鑰 )	-	2013-12-01