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B. Tubić

Društvene mreže:

B. Teofilović, E. Gligorić, Martina Ninić, S. Vukmirović, Ž. Gagić, N. Mandić-Kovačević, Biljana Tubić, Đorđe Đukanović, N. Grujić-Letić

The pharmacological potential of Lamiaceae plants is primarily linked to their high content of phenolic acids and flavonoids, known for strong antioxidant properties. This study investigated the antioxidant activity of ten widely used Lamiaceae herbs—oregano, lavender, basil, savory, garden thyme, wild thyme, sage, rosemary, lemon balm, and mint—prepared as traditional infusions and microwave-assisted extracts. The antioxidant capacity was evaluated using spectrophotometric assays, and total phenolics and flavonoids were quantified via spectrophotometry and HPLC. Chemometric analysis (PCA) was applied to explore correlations among antioxidant parameters. The results demonstrated excellent antioxidant activity across all samples. The IC50 for DPPH radicals was in the range from 3.73(0.13) to 8.03(0.17) μg/mL and that for ABTS radicals was from 2.89(0.12) to 8.55(0.34). The CUPRAC antioxidant assay delivered values in the range from 351.93(11.85) to 1129.68(44.46) μg TE/mg DE. The FRAP method produced values from 1.27(0.03) to 6.60(0.26) μmol Fe/mg DE. The presence of gallic acid was detected in all examined samples, with lemon balm and lavender exhibiting the highest concentrations across both applied extraction methods. Notably, lavender showed especially high levels of p-hydroxybenzoic acid and chlorogenic acid. Microwave-assisted extraction generally yielded higher levels of bioactive compounds compared to infusion. These findings highlight the potential of Lamiaceae herbal extracts, particularly those obtained through microwave-assisted extraction, as valuable sources of dietary antioxidants for everyday use.

Martin Kondža, J. Bukić, I. Čavar, Biljana Tubić

Cytochrome P450 (CYP450) enzymes are pivotal in the metabolism of numerous anticancer agents, with CYP3A4 being the predominant isoform involved. Inhibition of CYP450 enzymes is a major mechanism underlying clinically significant drug-drug interactions (DDIs), particularly in oncology, where polypharmacy is frequent. This review aims to provide a comprehensive and critical overview of CYP450 enzyme inhibition, focusing specifically on the impact of kinase inhibitors (KIs) and poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. A systematic review of the current literature was conducted, focusing on the molecular mechanisms of CYP450 inhibition, including reversible, time-dependent, mechanism-based, and pseudo-irreversible inhibition. Specific attention was given to the inhibitory profiles of clinically relevant KIs and PARP inhibitors, with analysis of pharmacokinetic consequences and regulatory considerations. Many KIs, such as abemaciclib and ibrutinib, demonstrate time-dependent or quasi-irreversible inhibition of CYP3A4, while PARP inhibitors like olaparib and rucaparib exhibit moderate reversible and time-dependent CYP3A4 inhibition. These inhibitory activities can significantly alter the pharmacokinetics of co-administered drugs, leading to increased risk of toxicity or therapeutic failure. Regulatory guidelines now recommend early identification of time-dependent and mechanism-based inhibition using physiologically based pharmacokinetic) (PBPK) modeling. CYP450 inhibition by KIs and PARP inhibitors represents a critical but often underappreciated challenge in oncology pharmacotherapy. Understanding the mechanistic basis of these interactions is essential for optimizing treatment regimens, improving patient safety, and supporting personalized oncology care. Greater clinical vigilance and the integration of predictive modeling tools are necessary to mitigate the risks associated with CYP-mediated DDIs.

Mladen Duran, R. Suručić, Biljana Tubić, R. Škrbić

Eryngium amethystinum L is a plant which grows in Balkan and Apennine peninsulas. The aerial parts, roots and fruits are used in ethnopharmacology of Italy and Western Balkan countries. Traditional preparations of E amethystinum were used in treatment of oedema, malaria and gastrointestinal diseases. Essential oils and extracts were isolated from aerial parts and roots of E amethystinum and examined by antimicrobial, antioxidative and cytotoxic assays. Gas-chromatography analysis showed predominance of germacrene D and spathulenol in essential oils of E amethystinum aerial parts, which have contributed to strong cytotoxic activity, while the methanolic extract exhibited strong antioxidative and antimicrobial activity. This article summarises all existing knowledge regarding E amethystinum, its chemical composition and pharmacological activity.

Radovan Kukobat, R. Škrbić, Fernando Vallejos-Burgos, E. Mercadelli, Davide Gardini, L. Silvestroni, C. Zanelli, Laura Esposito, Dragan M. Stevic et al.

High dissolution of anticancer drugs directly adsorbed onto porous carriers is indispensable for the development of drug delivery systems with high bioavailability. We report direct adsorption/loading of the anticancer drug letrozole (LTZ) onto the clinoptilolite (CLI) zeolite after the surface activation.In vitroLTZ dissolution from the CLI zeolites reached 95 % after 23 h in an acidic medium, being faster than the dissolution of the pure LTZ molecules. Fast dissolution occurs due to uniform exposure of the LTZ onto the external surface of the CLI zeolites, being accessible to the solvent for dissolution. On the other hand, the LTZ molecules were hidden in the bulk phase, giving a slow dissolution rate. Small positive value of the CLI/LTZ adsorption energy of 0.06 eV suggests that the release process is favourable in aqueous media. The main merit of the CLI/LTZ system is its quick onset of action and high bioavailability. This work demonstrates a possibility of enhancement of the dissolution of poorly soluble LTZ from the CLI zeolite, being promising for the further development of drug delivery systems.

B. Godman, M. Władysiuk, S. McTaggart, A. Kurdi, Eleonora Allocati, M. Jakovljevic, F. Kalemeera, Iris Hoxha, A. Nachtnebel et al.

[This corrects the article DOI: 10.1155/2021/9996193.].

Alice Pisana, B. Wettermark, A. Kurdi, Biljana Tubić, C. Pontes, C. Zara, E. van Ganse, G. Petrova, I. Mardare et al.

Background: Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care. This can support policy decisions including funding. Consequently, there is a need for improving datasets for establishing real-world outcomes of newly launched oncology medicines. Aim: To outline the types of available datasets for collecting patient-level data for oncology among different European countries. Additionally, to highlight concerns regarding the use and availability of such data from a health authority perspective as well as possibilities for cross-national collaboration to improve data collection and inform decision-making. Methods: A mixed methods approach was undertaken through a cross-sectional questionnaire followed-up by a focus group discussion. Participants were selected by purposive sampling to represent stakeholders across different European countries and healthcare settings. Descriptive statistics were used to analyze quantifiable questions, whilst content analysis was employed for open-ended questions. Results: 25 respondents across 18 European countries provided their insights on the types of datasets collecting oncology data, including hospital records, cancer, prescription and medicine registers. The most available is expenditure data whilst data concerning effectiveness, safety and outcomes is less available, and there are concerns with data validity. A major constraint to data collection is the lack of comprehensive registries and limited data on effectiveness, safety and outcomes of new medicines. Data ownership limits data accessibility as well as possibilities for linkage, and data collection is time-consuming, necessitating dedicated staff and better systems to facilitate the process. Cross-national collaboration is challenging but the engagement of multiple stakeholders is a key step to reach common goals through research. Conclusion: This study acts as a starting point for future research on patient-level databases for oncology across Europe. Future recommendations will require continued engagement in research, building on current initiatives and involving multiple stakeholders to establish guidelines and commitments for transparency and data sharing.

Biljana Tubić, S. Jungić

The use of the biological medicines, also called “biologics,” has contributed to the progress of the treatment of many chronic diseases, such as cancer, rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and psoriasis. However, biologicals are expensive for healthcare systems in several countries. Their availability has been a global issue, which has affected many patients that suffer from various diseases. A biosimilar medicine, also called “biosimilar,” is a medicine with similar characteristics in terms of quality, biological activity, safety, and efficacy as the approved original biological medicine, known as “originator biologic.” Biosimilars generate competition within the market because they lower the prices of biologics and thus allow for an increase in patient access. However, there are barriers when it comes to the acceptability rate of biosimilars and how interchangeable they are with the originator biologic. In this review, we present a national regulatory framework for biologics along with its limitations, a system of monitoring the safety profile of biologics, the guideline for interchangeability, and a list of approved and available biologics in Bosnia and Herzegovina. Additionally, recommendations were made here in order to provide opportunities for greater acceptance of biosimilars and better access to biologics. These recommendations include, but are not limited to, strengthening the national regulatory framework for biologics, capacity building, increasing awareness among healthcare providers for reporting adverse drug events and active pharmacovigilance, and better definitions of interchangeability. Finally, awareness among healthcare providers regarding biosimilars and biologics should be raised through continuous education and workshops, and by including this important topic in the graduate and postgraduate curriculum programs in the country.

B. Godman, Biljana Tubić, Eleonora Allocati, M. Władysiuk, S. McTaggart, Amanj Kurdi, M. Haque, S. MacBride-Stewart, F. Kalemeera et al.

Sales of medicines continue to grow world-wide driven in part by increasing expenditures on biological medicines leading to concerns with the long-term sustainability of European healthcare systems. The increasing use of biosimilars at lower costs can potentially address this. However, there can be concerns with their prescribing. There are also concerns with biosimilar insulin glargine including concerns with different devices despite increasing sales of long-acting insulin analogues worldwide. Consequently, a need to appraise the European biosimilar market incorporating measures to enhance their use including potential ways to increase the prescribing of biosimilars of insulin glargine at lower costs. Multiple approaches were used to undertake the study including researching measures to enhance biosimilar use and their impact across Europe. In addition, undertake cross national research on the utilization and expenditure of long-acting insulin analogues, which includes biosimilars, principally among Central and Eastern European countries. Multiple demand-side measures across the countries have enhanced the use of biosimilars. There was variable use of biosimilar insulin glargine 100 IU/ml driven by increasing use of patented 300 IU/ml formulations and small price differences between the originator and biosimilars in practice. Overall, multiple demand-side (cid:76)(cid:81)(cid:76)(cid:87)(cid:76)(cid:68)(cid:87)(cid:76)(cid:89)(cid:72)(cid:86)(cid:3)(cid:70)(cid:68)(cid:81)(cid:3)(cid:68)(cid:83)(cid:83)(cid:85)(cid:72)(cid:70)(cid:76)(cid:68)(cid:69)(cid:79)(cid:92)(cid:3)(cid:76)(cid:81)(cid:70)(cid:85)(cid:72)(cid:68)(cid:86)(cid:72)(cid:3)(cid:69)(cid:76)(cid:82)(cid:86)(cid:76)(cid:80)(cid:76)(cid:79)(cid:68)(cid:85)(cid:3)(cid:88)(cid:86)(cid:72)(cid:3)(cid:69)(cid:72)(cid:81)(cid:72)(cid:191)(cid:87)(cid:76)(cid:81)(cid:74)(cid:3)(cid:68)(cid:79)(cid:79)(cid:3)(cid:74)(cid:85)(cid:82)(cid:88)(cid:83)(cid:86)(cid:17)(cid:3)(cid:36)(cid:71)(cid:71)(cid:76)(cid:87)(cid:76)(cid:82)(cid:81)(cid:68)(cid:79)(cid:3)(cid:80)(cid:72)(cid:68)(cid:86)(cid:88)(cid:85)(cid:72)(cid:86)(cid:3)(cid:68)(cid:85)(cid:72)(cid:3)(cid:81)(cid:72)(cid:72)(cid:71)(cid:72)(cid:71)(cid:3)(cid:87)(cid:82)(cid:3)(cid:72)(cid:81)(cid:75)(cid:68)(cid:81)(cid:70)(cid:72)(cid:3)

J. Berendika, S. Jungić, Biljana Tubić, I. Rakita, Milka Vještica, Dejan Đokanović, Z. Gojković, Nikolina Mirčeta, Sanja Petković et al.

Background / Aim: Up until ten years ago stage four melanoma was considered a disease with extremely poor prognosis. Standard therapy during this period of time was dacarbazine chemotherapy. Patients with better performance status were treated with immunotherapy cytokine IL-2. In the last ten years eight medications have been approved by the FDA for the therapy of melanoma. The goal of this study was to determine objective response rate (ORR), median overall survival (OS), median progression free survival (PFS) and safety in patients with advanced and metastatic cutaneous melanoma treated with targeted therapy and immunotherapy at the University Clinical Centre of the Republic of Srpska (Centre). Methods: A non-randomised observational retrospective/prospective trial was conducted to investigate first experiences with the use of targeted therapy and immunotherapy at the Centre and compare the results with the literature data. A total of 23 patients received BRAF targeted therapy for the treatment of metastatic cutaneous melanoma in the first line of treatment. Nine patients received vemurafenib, fourteen patients received a combination of BRAF/MEK inhibitor. Nine patients were treated with pembrolizumab immunotherapy. The trial was performed in a period from May 2017 until December 2020. Results: In patients receiving vemurafenib ORR was 44.4 %, median PFS was 5 months (95 % CI, 1 to 11) and the median OS was 9 months (95 % CI, 2 to 17). In the vemurafenib/cobimetinib group ORR was 71.4 %. Median PFS was 9 months and median OS was 12 months. ORR in patients receiving pembrolizumab was 22.9 %, median PFS was 3 months (95 % CI, 1 to 11) and the median OS was 4.5 months (95 % CI, 2 to 12). Results in all three groups were inferior compared to the results from the literature except for ORR in patients receiving vemurafenib and vemurafenib/cobimetinib. Adverse events were tolerable and manageable and were similar to those described in the literature. Conclusion: Based on the experience with the targeted and immunotherapy in the Centre, which was presented in this study, it was concluded that in conditions when there is limited access to drugs, the greatest benefit have the patients who meet the inclusion criteria in clinical trials.

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