Pharmazie最新文献

The history of the Croatian pharmaceutical company PLIVA from the very beginning to the status of a recognisable European and global player is described. Special attention is paid to PLIVA's cooperation with the Croatian Nobel laureate Vladimir Prelog and the invention of the proprietary antibiotic azithromycin. The antibiotic was commercialised in cooperation with the US-based company Pfizer. PLIVA's predecessor was Kaštel, Factory for Chemico-Pharmaceutical Products Joint-Stock Company. It was founded in 1920 in Karlovac, Croatia to continue operation in Zagreb in 1928. Eventually it was incorporated into the State Institute for the Production of Medicines and Vaccines bearing the acronym PLIVA (1942). In 1952, thanks to the collaboration with the organic chemist and 1975 Nobel Prize laureate Vladimir Prelog, the PLIVA Research Institute was founded. Thirty years later the research conducted by a team of scientists led to the invention of azithromycin, a new antibiotic, first member of azalides, a new class of macrolides. The core team working on azithromycin synthesis, development and patent protection (priority patent applications submitted in 1979 and 1981) included Dr Slobodan Đokić, Gabrijela Kobrehel, MSc, Dr Gorjana Lazarevski, and Dr Zrinka Tamburašev. Azithromycin was marketed globally under the trademarks of Sumamed® (PLIVA, 1988) and Zithromax® (Pfizer, 1991). It has become and still is one of the most successful and best-selling antibiotics in the world. The story of PLIVA and azithromycin shows that blockbusters can be invented based on dedication, knowledge and long-time experience despite possibly unfavourable conditions.

The Hellenic Pharmacopoeia, authored by Ottoman pharmacist Georgios Photeinos and published in 1835 in Smyrna (modern-day Izmir, Türkiye), is a historically significant yet largely overlooked work in 19th-century pharmaceutical literature. At a time when modern pharmaceutical resources in Greek were scarce, Photeinos sought to address this gap by creating a comprehensive pharmacopoeia that extensively drew from the Austrian Pharmacopoeia, as well as French and Latin sources. Although he initiated the project around 1804, political upheavals delayed its completion by more than three decades. Spanning 538 pages, the Hellenic Pharmacopoeia is divided into three sections: a Lexicon of Pharmacopoeia, a Synopsis of the Theory of Chemistry, and a section on Practice of the Pharmacopoeia, or the Preparation. In the lexicon, Photeinos included Turkish terms written in the Greek alphabet, reflecting his commitment to making the work accessible to Turkish-speaking Greek communities within the Ottoman Empire. Despite its ambition, Photeinos' work was overshadowed by the official pharmacopoeia of Greece, published in Athens in 1837 under the same title, Hellenic Pharmacopoeia. His efforts to modernize and standardize pharmaceutical practices for Greek-speaking communities represents an important step toward the professionalization during a period of significant socio-political transformation. This paper examines Photeinos' life, contributions, and the significance of his pharmacopoeia, which has remained largely forgotten.

This study aimed to determine the risk of emergency admission by ambulance in patients taking potentially inappropriate medications (PIMs). We included 273,932 patients aged over 75 years of age admitted between January 1, 2019, and December 31, 2019, using the Japan Medical Data Center medical insurance database containing anonymized patient data. We excluded patients without a history of admission. In total, 22,017 patients were included in the analysis. The commonly prescribed PIMs were diuretics, benzodiazepines, non-benzodiazepines, H2 receptor blockers, and nonsteroidal anti-inflammatory drugs. The primary endpoint, which was the incidence rate of emergency admission by ambulance after discharge, was 31.5/100,000 person-days in patients aged over 75 years. The secondary endpoints, which were risk factors for admission, included the use of PIMs, age over 85 years, male sex, history of congestive heart failure, history of chronic respiratory disease, and the number of medications at discharge. In contrast, body mass index was observed to have a negative trend in relation to admission. In conclusion, we observed 31.5/100,000 person-days of emergency admission by ambulance after discharge in patients aged over 75 years. Administration of PIMs upon discharge poses a risk for admission. To avoid emergency admissions via ambulances, it is important to discontinue or reduce the prescription of PIMs while considering the risks and benefits for each patient.

Cigarette smoke extract (CSE)-induced airway mucus hypersecretion and inflammation are prominent features of chronic obstructive pulmonary disease (COPD). As a factor associated with inflammation regulation, T cell immunoglobulin and mucin domain-1 (TIM-1) is found to be involved in various inflammatory disorders such as asthma and COPD. In this study, the GEO database provides two human COPD gene expression datasets (GSE67472, n = 62) along with the relevant controls (n = 43) for differentially expressed gene (DEG) analyses. Candidate biomarkers are identified, and the discriminatory ability is determined using the area under the receiver operating characteristic curve (AUC) values. Furthermore, a COPD mouse model is established using CSE to validate that anti-TIM-1 can attenuate airway mucus hypersecretion and inflammation via the PI3K/Akt signaling pathway in COPD. Anti-TIM-1 antibody pretreatment significantly suppresses mucin secretion, inflammatory cell infiltration, and inflammatory cytokine release in mouse lungs induced by CSE and also suppresses CSE-induced expression of MUC5AC. Western blot shows that the anti-TIM-1 antibody attenuates the activation of p-Akt in airway mucus hypersecretion mice induced by CSE. This study highlights the protective effect of the TIM-1 antibody on CSE-related airway mucus hypersecretion and inflammation, in which PI3K/AKT may be involved. These findings suggest that TIM-1 could be a potential therapeutic target for airway mucus hypersecretion.

The COVID-19 pandemic caused global pandemonium, and due to an unprecedented global response, the popularity and use of (veterinary) ivermectin, amongst many other conceivable 'treatments', experienced a meteoric rise. Ivermectin is a macrocyclic lactone compound belonging to the avermectin drug class and is a registered medicine in many countries, although the most common use is as veterinary medicine. In this study, a fast HPLC method was developed and validated for the quantification of ivermectin in veterinary products that were used off-label by a substantial number of people during COVID-19. Locally used veterinary products were collected as well as commercial products acquired and were tested using the newly developed method. The ivermectin content was compared to the products' label claims and it was found that all products tested contained ivermectin within acceptable limits. However, the use of veterinary products is strongly discouraged due to high dosages and administration regimens that were tested in animals and can lead to serious adverse events in humans. The presence of untested excipients and secondary actives, such as clorsulon, which can cause unknown (long-term) health impacts in humans, further adds credence to this warning.

Background and aim: Interprofessional education of medical and pharmacy students may improve competence-based university teaching. Investigations: We developed a joint bed-side teaching to improve patient-related competencies in identifying drug-related problems in hospitalized patients at a university cardiology department. Students were randomly allocated in mixed teams of medical and pharmacy students (1:3). The concept consisted of four parts: (i) kick-off session (day 1), (ii) file analysis and bed-side patient interview (day 2), (iii) medication analysis (free time management), and (iv) presentation of the acquired results (day 3). Expectations and competencies, predefined in 10 categories and 10 assessment levels (0-none to 10-maximum), were evaluated before and after the course (degree of fulfillment of the expectations reported after the course). Results: Overall, 12 students participated, eight of whom were female. Median age was 23 years (Q25/Q75: 22/24). The median time at university was 8 semesters (Q25/Q75: 7/9). The competencies were assessed by the students before and after the course in the following categories: Competencies in "Treatment of diseases" (median rating before/after the course: 6/7; n.s.), "Diagnostics of diseases" (4.5/5; n.s.), "Future physician-pharmacist cooperation" (6/8; p=0.005), "Interaction with patients" (6.5/7; n.s.), "Cardiology" (5/7; p=0.012), "Interprofessional student communication" (6.5/9; p=0.005), "Dealing with patient-oriented questions" (6.5/8; n.s.), "Future professional life" (5/7.5; p=0.012), "Practical problem solving" (6/7; p=0.027), "Scientific work" (6/7.5; n.s.). Expectations before the course were highest (median of 10) in the categories "Future physician-pharmacist cooperation", "Dealing with patient-oriented questions", "Future professional life", and "Practical problem solving". The highest levels of expectation fulfilment were reported after the course for the categories "Future physician-pharmacist cooperation" and "Interprofessional student-communication". In the free text, interprofessional collaboration was frequently mentioned as a particularly positive aspect of the course. Conclusions: A pilot joint bed-side teaching course for medical and pharmacy students was feasible and an early interprofessional collaboration during medical and pharmacy studies may improve several competencies particularily regarding competencies in physician-pharmacist cooperation and in interprofessional student communication.

Background: Major Depressive Disorder (MDD) is a prevalent and debilitating mental disorder that has been linked to hyperhomocysteinemia and folate deficiency. These conditions are influenced by the methylenetetrahydrofolate reductase (MTHFR) gene, which plays a crucial role in converting homocysteine to methionine and is essential for folate metabolism and neurotransmitter synthesis, including serotonin. Study aim: This study explored the association between MTHFR C677T and A1298C polymorphisms among Saudi MDD patients attending the Erada Complex for Mental Health and Erada Services outpatient clinic in Jeddah, Saudi Arabia. Methods: The study involved 87 MDD patients and 87 control subjects. Saliva samples were collected, and genomic DNA was extracted. Polymerase chain reaction-restriction fragment length polymorphism was used to detect MTHFR gene polymorphisms. Results: A significant difference was observed in the distribution of genotype frequencies for MTHFR C677T and A1298C polymorphisms between MDD patients and controls in the Saudi cohort (C677T: P = 0.001; A1298C: P = 0.01) Risk analysis indicated that individuals with the mutant TT genotype of the C677T polymorphism (Odd Ratio (OR) = 6.80, CI 95% = 1.47-31.36, P = 0.01) and the mutant CC genotype of the A1298C polymorphism (OR = 2.64, CI 95% = 1.36-5.13, P = 0.004) are more common in MDD patients, suggesting a higher risk for depression. Gender-specific analyses showed that the MTHFR C677T TT genotype significantly increases the risk of MDD in males compared to females. Conclusion: These findings underscore the significant impact of genetic factors, particularly the association of MTHFR polymorphisms with MDD. The results highlight the importance of personalized treatment approaches considering individual genetic profiles.

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

Tapentadol is a unique opioid analgesic due to its dual mechanism of action. Compared to other opioids with a classical mechanism of action, its analgesic potential is not far behind them, and its advantages are: a better safety profile in terms of a lower potential for drug-drug interactions and a lower potential for causing adverse events, and it is safe to use in sensitive populations. Tapentadol in the form of a immediate release formulation is an adequate drug of choice for achieving a pharmacotherapeutic analgesic response in acute pain conditions, while in the form of a extended release formulation it is an adequate pharmacotherapeutic analgesic solution for chronic pain syndromes of various etiology. Due to the specificity of the mechanism of action, tapentadol adequately relieves both pain components - nociceptive and neuropathic, and has an indication area for mixed pain syndrome as well. Based on this, the need for the use of co-analgesics is reduced, and thus the incidence of possible interactions and adverse events is reduced.

After repeated inquiries from patients whether sulfonamide antibiotic allergy should be considered in the context of taking a triptan, we present here the pharmaceutical background, the chemical structure of triptans, and the clinical relevance in a narrative review. In fact, evidence-based cross-reactivity referring to the well-known allergic reaction of sulfonamide antibiotics has not been described so far.