• Klíčová slova
• Clostilbegyt, Femara, Dracenax, Lerana,
• MeSH
• anovulace * etiologie   farmakoterapie   MeSH
• gonadotropiny aplikace a dávkování   ekonomika   farmakologie   MeSH
• indukce ovulace ekonomika   metody   MeSH
• inhibitory aromatasy aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• klomifen aplikace a dávkování   farmakologie   MeSH
• letrozol aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• lidé MeSH
• náklady na léky MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• ženská infertilita etiologie   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. PATIENTS AND METHODS: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. RESULTS: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.

• MeSH
• Evropská unie MeSH
• individualizovaná medicína * metody   MeSH
• klinické zkoušky jako téma organizace a řízení   MeSH
• lidé MeSH
• nádory * terapie   MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.

• MeSH
• diabetes mellitus 2. typu * MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• krevní glukóza MeSH
• lidé MeSH
• management nemoci MeSH
• metformin * farmakologie   terapeutické užití   MeSH
• nemoci parodontu * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Repurposing of authorised medicines has been under discussion for a long time. Drug repurposing is the process of identifying a new use for an existing medicine in an indication outside the scope of the original approved indication. Indeed, the COVID-19 health crisis has brought the concept to the frontline by proving the usefulness of this practise in favour of patients for an early access to treatment. Under the umbrella of the Pharmaceutical Committee and as a result of the discussions at the European Commission Expert Group on Safe and Timely Access to Medicines for Patients (STAMP) a virtual Repurposing Observatory Group (RepOG) was set up in 2019 to define and test the practical aspects of a pilot project thought to provide support to "not-for-profit" stakeholders generating or gathering data for a new therapeutic use for an authorised medicine. The group's initial plan was impacted by the outbreak of the SARS-CoV-2 pandemic and the launch of the pilot needed to be postponed. This article describes the progress and the activities conducted by the group during this past and yet extraordinary 2020-2021 to keep the project alive and explores on the background of this topic together with the obvious opportunities this health crisis has brought up in terms of repurposing of medicines.

• Publikační typ
• časopisecké články MeSH

All over the world, high drug prices prevent some people to be adequately treated. The price is caused, at least in part, by the complexity of the current drugs and high costs of their discovery and development. The present article reviews some possibilities how to reduce the cost by developing me-too drugs, using repurposing strategy and, last but not least, by generic substitution. The main part of the article deals with the Four Thieves Vinegar initiative offering information necessary for production of Do-It-Yourself (DIY) medicines. All drawbacks of the strategy are discussed.

• MeSH
• chemie farmaceutická normy   MeSH
• dostupnost zdravotnických služeb ekonomika   organizace a řízení   zákonodárství a právo   MeSH
• generika MeSH
• náhrada léků MeSH
• náklady na léky MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• příprava léků metody   normy   MeSH
• schvalování léčiv MeSH

Drug repositioning is a successful approach in medicinal research. It significantly simplifies the long-term process of clinical drug evaluation, since the drug being tested has already been approved for another condition. One example of drug repositioning involves cardiac glycosides (CGs), which have, for a long time, been used in heart medicine. Moreover, it has been known for decades that CGs also have great potential in cancer treatment and, thus, many clinical trials now evaluate their anticancer potential. Interestingly, heart failure and cancer are not the only conditions for which CGs could be effectively used. In recent years, the antiviral potential of CGs has been extensively studied, and with the ongoing SARS-CoV-2 pandemic, this interest in CGs has increased even more. Therefore, here, we present CGs as potent and promising antiviral compounds, which can interfere with almost any steps of the viral life cycle, except for the viral attachment to a host cell. In this review article, we summarize the reported data on this hot topic and discuss the mechanisms of antiviral action of CGs, with reference to the particular viral life cycle phase they interfere with.

• MeSH
• antivirové látky farmakologie   terapeutické užití   MeSH
• COVID-19 MeSH
• digitoxin MeSH
• digoxin MeSH
• internalizace viru účinky léků   MeSH
• lidé MeSH
• nádory farmakoterapie   MeSH
• ouabain MeSH
• pandemie MeSH
• přehodnocení terapeutických indikací léčivého přípravku metody   MeSH
• replikace viru účinky léků   MeSH
• SARS-CoV-2 MeSH
• sodíko-draslíková ATPasa MeSH
• srdeční glykosidy metabolismus   terapeutické užití   MeSH
• srdeční selhání farmakoterapie   virologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The concept of hierarchical organization of tumour cell population, with cancer stem cells positioned at the apex of the cell hierarchy, can explain at least some crucial aspects of biological and clinical behaviour of cancer, like its propensity to relapse as well as the development of therapeutic resistance. The underlying biological properties of cancer stem cells are crucially dependent on various signals, inhibition of which provides an attractive opportunity to attack pharmacologically cancer stem cells. Currently, a lot of such stemness-inhibitors undergo various phases of clinical testing. Interestingly, numerous old drugs that are in routine use in human and veterinary medicine for non-oncological indications appear to be able to specifically target cancer stem cells as well. As cancer stem cells, at least for most tumours, represent usually only a minor tumour cell fraction, it is quite probable that the main focus of the clinical use of the stemness inhibitors would consist in their rational combinations with traditional anticancer treatment modalities. A highly important goal for the future research is to identify reliable and clinically applicable predictive markers that would allow to apply these novel anticancer drugs on the individual basis within the context of personalized medicine.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• individualizovaná medicína MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• nádorové kmenové buňky účinky léků   MeSH
• nádory farmakoterapie   MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Východiska: Metformin je lékem první volby u diabetiků, lékem stále šířeji využívaným i v nediabetické populaci, a to zejména díky kombinaci efektivity a excelentního bezpečnostního profilu. Nad rámec známých metabolických efektů prokázaly retrospektivní epidemiologické studie, že užívání metforminu u diabetiků snižuje riziko vzniku nádorů a/nebo zlepšuje prognózu ve srovnání s těmi, kteří užívají jiná antidiabetika. Toto je velmi silný argument pro to, uvažovat o změně účelu indikace metforminu jako případného adjuvancia v onkologických indikacích, nicméně je bezpodmínečně nutné ověřit tuto domněnku v duchu medicíny založené na důkazech. Metformin patří mezi biguanidy a v kontextu diabetu typu 2 zvyšuje citlivost tkání k inzulinu. Účinkuje především na úrovni jater, kde inhibuje oxidativní fosforylaci, což vede k supresi glukoneogeneze a způsobuje pokles koncentrace glukózy v krvi. Působí také na svalové a tukové buňky, ve kterých zlepšuje utilizaci glukózy. Mechanizmy zodpovědné za protinádorový účinek metforminu jsou detailně studovány a zdá se, že nejdůležitější je jeho schopnost vyvolat intracelulární energetický stres a následně metabolické změny, které mají cytostatický nebo cytotoxický efekt. Rozsáhlá klinická zkušenost s metforminem v léčbě diabetu v kombinaci s jeho prokázaným efektem na různé typy nádorových buněk vedla k zahájení mnoha klinických studií, které testovaly jeho potenciál při léčbě nádorů. Cíl: Cílem této práce je shrnout současné znalosti o protinádorových účincích metforminu a výsledky recentních klinických studií s metforminem při léčbě různých typů nádorů.

Background: Metformin is the most commonly used antidiabetic drug with a plethora of proven metabolic and cardiovascular beneficial effects and exceptional safety profile. On top of the established metabolic effects, retrospective epidemiologic evidence shows that metformin use is associated with decreased cancer risk and/or improved disease prognosis in diabetic cancer patients on metformin compared to those treated with different antidiabetic drugs. This is a sound argument for eventual repurposing metformin as an adjuvant drug in oncology; however, evidence-based data are currently needed to establish this. Metformin is a biguanide that in the context of type 2 diabetes primarily targets the liver. Metformin inhibits oxidative phosphorylation which leads to the suppression of gluconeogenesis and causes decrease of blood glucose concentration. Mechanisms responsible for metformin anti-neoplastic effect have been investigated extensively, and key events seem to centralize around its ability to induce intracellular energetic stress with subsequent changes of metabolism resulting in cytostatic or cytotoxic action. Large clinical experience with metformin in the treatment of diabetes together with its plausible effects on different cancer cell types initiated a number of clinical trials that tested the hypothesis that metformin might have a beneficial effect in the treatment of cancer. Purpose: The aim of this review is to compile recent advances in our understanding of metformin antineoplastic effects and to give a summary of the results of recent clinical trials of metformin for treatment of different cancer types.

• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• diabetes mellitus farmakoterapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• metformin * farmakologie   terapeutické užití   MeSH
• nádory farmakoterapie   MeSH
• Check Tag
• lidé MeSH

The control of gastrointestinal nematodes (GINs), the most abundant and serious parasites of livestock, has become difficult because of the limited number of available drugs and fast development of drug resistance. Thus, considerable efforts have been devoted to developing new anthelmintics that are efficient against nematodes, especially resistant species. Here, we summarize the most recent results using various approaches: target-based or high-throughput screening (HTS) of compound libraries; the synthesis of new derivatives or new combinations of current anthelmintics; the repurposing of drugs currently approved for other indications; and lastly, the identification of active plant products. We also evaluate the advantages and disadvantages of each of these approaches.

• MeSH
• anthelmintika chemie   terapeutické užití   MeSH
• biologické přípravky terapeutické užití   MeSH
• fixní kombinace léků MeSH
• gastrointestinální nemoci farmakoterapie   veterinární   MeSH
• lidé MeSH
• nematodózy farmakoterapie   veterinární   MeSH
• objevování léků MeSH
• přehodnocení terapeutických indikací léčivého přípravku MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

OBJECTIVES: To evaluate the access to comprehensive diagnostics and novel antituberculosis medicines in European countries. METHODS: We investigated the access to genotypic and phenotypic Mycobacterium tuberculosis drug susceptibility testing and the availability of antituberculosis drugs and calculated the cost of drugs and treatment regimens at major tuberculosis treatment centres in countries of the WHO European region where rates of drug-resistant tuberculosis are the highest among all WHO regions. Results were stratified by middle-income and high-income countries. RESULTS: Overall, 43 treatment centres from 43 countries participated in the study. For WHO group A drugs, the frequency of countries with the availability of phenotypic drug susceptibility testing was as follows: (a) 75% (30/40) for levofloxacin, (b) 82% (33/40) for moxifloxacin, (c) 48% (19/40) for bedaquiline, and (d) 72% (29/40) for linezolid. Overall, of the 43 countries, 36 (84%) and 24 (56%) countries had access to bedaquiline and delamanid, respectively, whereas only 6 (14%) countries had access to rifapentine. The treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was available only in 17 (40%) of the 43 countries. The median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for 6 months), and extensively drug-resistant tuberculosis (including bedaquiline, delamanid, and a carbapenem) were €44 (minimum-maximum, €15-152), €764 (minimum-maximum, €542-15152), and €8709 (minimum-maximum, €7965-11759) in middle-income countries (n = 12) and €280 (minimum-maximum, €78-1084), €29765 (minimum-maximum, €11116-40584), and €217591 (minimum-maximum, €82827-320146) in high-income countries (n = 29), respectively. DISCUSSION: In countries of the WHO European region, there is a widespread lack of drug susceptibility testing capacity to new and repurposed antituberculosis drugs, lack of access to essential medications in several countries, and a high cost for the treatment of drug-resistant tuberculosis.

• MeSH
• antituberkulotika terapeutické užití   MeSH
• extenzivně rezistentní tuberkulóza * mikrobiologie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• multirezistentní tuberkulóza * farmakoterapie   mikrobiologie   MeSH
• Mycobacterium tuberculosis * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH