Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
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Item A Comprehensive Examination of UV-VIS Spectrophotometric Methods in Pharmaceutical Analysis Between 2015-2023(Başkent Üniversitesi Eczacılık Fakültesi, 2024-06) Enes, Duygu; Dastan, Kerem; Kaplan, Ozan; Celebier, Mustafa; Dogan, AysegulBackground: Quality control is a system of validated procedures in which many samples, including active pharmaceutical ingredients and final products, are analyzed using standard or validated analytical methods. Method: Analytical methods used in analyzing active pharmaceutical ingredients or final products in the pharmaceutical industry can be methods registered in pharmacopeias and developed by the company itself. For this reason, published papers related to pharmaceutical analysis attract analysts and researchers' attention. In this study, pharmaceutical analysis and bioanalysis studies carried out between 2015 and 2023 were examined using Google Scholar, and the recent trends were determined for pharmaceutical analysis. Among the published papers performing conventional analytical techniques for pharmaceutical analysis, those applying UV-VIS spectrophotometry method were selected to predict a future perspective in this study. In addition to the data obtained, the current situation of the pharmaceutical industry was considered to correlate with the obtained data for pharmaceutical analysis. Results: The results were presented with comparative tables and summarizing graphs. Interpreting the results allowed us to determine the trends that pharmaceutical analysis studies will lead in the future. This study can be helpful for researchers working on pharmaceutical analysis in both the industry and academia to predict future trends in pharmaceutical analysis. As a result of the literature research covering the dates 2015-2023, 56% of UV-VIS Spectrophotometric methods are used on pharmaceutical dosage forms, 27% are bulk, 16% are pure, 2% are biological materials, and 0.4% are herbal. Made from materials. Of these studies, 28% were conducted in the 200-240 nm range, 27% were conducted in the 240-300 nm range, and only 44% were conducted at >300 nm. Interpreting the results allowed us to determine the trends that pharmaceutical analysis studies will lead in the future. Conclusion: This study can be helpful for researchers working on pharmaceutical analysis in both the industry and academy side to predict future trends for pharmaceutical analysis.Item An Essential Component Of Antimicrobial Stewardship During The COVID-19 Pandemic In The Intensive Care Unit: De-Escalation(Başkent Üniversitesi Eczacılık Fakültesi, 2024-05-24) Pehlivanli, Aysel; Ozgun, Cigdem; Sasal-Solmaz, Firdevs Gonca; Yuksel, Didem; Basgut, Bilgen; Ozcelikay, Arif Tanju; Unal, Mustafa NecmettinBackground The antimicrobial de-escalation strategy (ADE) plays a crucial role in antimicrobial stewardship, reducing the likelihood of bacterial resistance. This study aims to evaluate how often the intensive care unit (ICU) used ADE for empirical treatment during COVID-19.Materials Adult ICU patients receiving empirical antimicrobial therapy for bacterial infections were retrospectively studied from September 2020 to December 2021. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of the antimicrobial to narrow the antimicrobial spectrum within the first 3 days of therapy, according to the test results and clinical picture.Results A total of 99 patients were included in the study. The number of patients who received empirical combined therapy (38.4%) was lower than those who received monotherapy (61.6%). The most preferred monotherapy (45.9%) was piperacillin-tazobactam, while the most preferred in combination treatment (22.7%) was meropenem. Within the first 3 days of admittance to the ICU, 3% of patients underwent ADE for their empirical antimicrobial therapy, 61.6% underwent no change, and 35.4% underwent change other than ADE. Procalcitonin levels were below 2 mu g/L on the third day of treatment in 69.7% of the patients. Culture or culture-antibiogram results of 50.5% of the patients were obtained within the first 3 days of empirical therapy. There was no growth in the culture results of 21 patients (21.2%) during their ICU stay.Conclusion In this study, ADE practice was much lower than expected. In order to reduce the significant differences between theory and reality, clinical, laboratory, and organisational conditions must be objectively assessed along with patient characteristics.Item Determination Of Drug-Related Problems According To Pair Criteria In Dialysis Patients: A Cross-Sectional Study In Tertiary Care Hospital(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-25) Pehlivanli, Aysel; Eren, Sayeste Akkan; Sengul, Sule; Basgut, Bilgen; Erturk, Sehsuvar; Ozcelikay, A. TanjuBackground Dialysis patients are at high risk for drug-related problems (DRPs), which have significant consequences for their morbidity, mortality, and quality of life. Improved clinical outcomes can be achieved by preventing, identifying, and resolving these problems. Methods This is a retrospective observational study. In this study, the PAIR instrument (Pharmacotherapy Assessment in Chronic Renal Disease) was validated for use in Turkish. Validation consisted of three stages: translation back-translation with expert panel evaluation, reliability analysis using the test-retest method, and conceptual validity with both Pharmaceutical Care Network Europe (PCNE) and PAIR used to determine DRPs prevalence. Results In total, 104 patients (mean +/- SD age, 54.1 +/- 15.8 years; 53.8% male) were included in the study. An expert panel evaluated the items in the criterion based on their intelligibility, service of purpose, differentiation, and cultural suitability during the translation stage. Content validity index (CVI) score was found to be 0.95. The reliability analysis was performed by applying the test-retest method and calculating correlation coefficient on 30 randomly selected patients one month later. Correlation coefficient (p) was found to be 0.8. To evaluate conceptual validity, 104 patients' pharmacotherapy plans were assessed using both the PAIR and PCNE criteria. The prevalence of DRPs according to PAIR criteria (100.0%) and PCNE (73.1%) were statistically significantly different (p < 0.001). Conclusions As a result, PAIR criteria can identify clinically relevant DRPs in patients with CKD and is a new, validated tool to be used in Turkey, but may not be adequate for patients receiving dialysis. Therefore, it needs to be reviewed and updated for dialysis patients.Item Ceftobiprole Mono-Therapy Versus Combination Or Non-Combination Regimen Of Standard Antibiotics For The Treatment Of Complicated Infections: A Systematic Review And Meta-Analysis(Başkent Üniversitesi Eczacılık Fakültesi, 2024-06-10) Jame, Wissal; Basgut, Bilgen; Abdi, AbdikarimObjective: Various bacteria produce complicated infections that are difficult to treat worldwide. Ceftobiprole is effective against resistant Gram-positive and Gram-negative bacteria. Methods: This review assessed effectiveness and safety of ceftobiprole monotherapy for severe infections. A systematic review and meta-analysis of randomized controlled trials comparing clinical cure, microbiological cure, and safety of ceftobiprole alone to a combination or non-combination antibiotic regimen was conducted. Until December 20, 2022, we searched a major databases. Results: This study includes 4168 patients from six trials. Ceftobiprole and comparator-received patients had similar clinical responses for all patient population. Also, the eradication rate of all organisms and specific pathogenic bacteria in microbiologically examined patients was comparable between the groups. Ceftobiprole induced more gastrointestinal side events than comparable drugs, mostly nausea [OR 1.91 (1.26-2.90), p = < 0.01]. While skin-related adverse events were significantly associated with comparator antibiotics [6 trials, 4062 patients; OR 0.77 (0.60-0.99), p=0.03]. Conclusion: Ceftobiprole monotherapy is effective and safe for severe infections caused by Gram-positive or Gram-negative bacteria.Item Azoles Display Promising Anticonvulsant Effects Through Possible Ppar-Α Activation(Başkent Üniversitesi Eczacılık Fakültesi, 2024-05-25) Sari, Suat; Yurtoglu, Sibel; Zengin, Merve; Marcinkowska, Monika; Siwek, Agata; Sarac, SelmaAzoles such as nafimidone, denzimol and loreclezole are known for their clinical efficacy against epilepsy, and loreclezole acts by potentiating gamma-aminobutyric acid (GABA)-ergic currents. In the current study, we report a series of azole derivatives in alcohol ester and oxime ester structure showing promising anticonvulsant effects in 6 Hz and maximal electro shock (MES) models with minimal toxicity. The most promising of the series, 5f, was active in both 6 Hz and MES tests with a median effective dose (ED50) of 118.92 mg/kg in 6 Hz test and a median toxic dose (TD50) twice as high in mice. The compounds were predicted druglike and blood-brain barrier (BBB) penetrant in silico. Contrary to what was expected, the compounds showed no in vitro affinity to GABAA receptors (GABAARs) in radioligand binding assays; however, they were found structurally similar to peroxisome proliferator-activated receptors alpha (PPAR-alpha) agonists and predicted to show high affinity and agonist-like binding to PPAR-alpha in molecular docking studies. As a result, 5f emerged as a safe azole anticonvulsant with a wide therapeutic window and possible action through PPAR-alpha activation.Item Comparative Plant Metabolomics of Momordica charantia Seeds and Fruits(Başkent Üniversitesi Eczacılık Fakültesi, 2024-03-30) Enes, Duygu; Fidan, Bilge Basak; Basaran, Arif Ahmet; Celebier, MustafaMomordica charantia L., Cucurbitaceae, known mainly as karela, bitter gourd or bitter melon, and balsam pear, is used for antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer, and anti-inflammatory and wound healing. This study aimed to elucidate the differences in the metabolites of 70% methanol extracts of M. charantia seeds and fruit using untargeted metabolomics. Liquid chromatography coupled to quadrupole time-of-flight mass spectrometry-based analysis of the extracts for both seed and fruit was performed using a C-18 column. Differences were observed in seed and fruit extracts, which were visualized using principal component analysis plots. (R)-Salsolinol, pantetheine, coumarin, tryptamine, lysophospholipidPC(O-18:0), glucosylceramide, pyroglutamic acid, and presqualene diphosphate in the seed and fruit of M. charantia were detected in different levels. The amount of lysophospholipidPC(O-18:0) (lysoPC(O-18:0)) and glucosylceramide is high in the fruit, while the amount of (R)-salsolinol, pantetheine, coumarin, tryptamine, presqualene diphosphate, and pyroglutamic acid is high in the seed. These primary untargeted metabolomic results revealed that the different pharmacological effects may be related to the variable amounts of some specific metabolites in seeds and fruits.Item Azole Rings Linked To Cox Inhibitors Via Hydrazone Bridge: Synthesis, Stereochemical Analysis, And Investigation Of Antimicrobial Activity(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-19) Karaguzel, Ayse; Ugur, Suemeyye Buran; Cetinkaya, Yasin; Dogan, Senguel Dilem; Stevanovic, Milena; Nikodinovic-Runic, Jasmina; Gunduz, Miyase GozdeNonsteroidal anti-inflammatory drugs (NSAIDs) alleviate inflammation and pain through the inhibition of cyclooxygenase (COX) enzymes. Besides these widely recognized therapeutic utilizations, NSAIDs have been reported to display moderate antimicrobial activity and enhance antimicrobial efficacy when administered in combination with commercial antimicrobial drugs. In the present study, we designed novel potential antimicrobial agents by linking some NSAIDs (ibuprofen, flurbiprofen, and naproxen) to various azole rings (pyrazole, imidazole, triazole, and benzimidazole) via hydrazone functionality. The hydrazone linker was introduced into the chemical scaffold of the title molecules by the reaction between hydrazides obtained from NSAIDs and inhouse synthesized azole-carrying benzaldehydes. The structures of the target compounds were elucidated by a combination of spectral methods. The NOESY spectra and stereochemical analyses performed using DFT method confirmed the presence of the target molecules as a mixture of E(C=N)-E(N-N)-synperiplanar and E(C=N)-E(N-N)antiperiplanar conformers in DMSO-d6 solution. 1H and 13C NMR chemical shift values in DMSO were calculated using the GIAO method and compared with the experimental NMR data. Finally, some derivatives were demonstrated to inhibit Candida albicans filamentation and/or bacterial communication system known as quorum sensing. For COX inhibitor-azole hybrids with antimicrobial potency, naproxen appeared to be the most appropriate NSAID, while bulky benzimidazole was not found as a preferable azole ring.Item The Clinical Efficacy of Adding Ceftazidime/Avibactam to Standard Therapy in Treating Infections Caused by Carbapenem-Resistant Klebsiella pneumonia with blaOXA-48-like Genes(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-03) Jaber, Al Maamon R. Abu; Basgut, Bilgen; Hawan, Ali Abdullah; Al Shehri, Ali Amer; AlKahtani, Sultan Ahmad; Ahmed, Nehad J.; Abdi, AbdikarimCeftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.Item Antimicrobial Dosing Recommendations During Continuous Renal Replacement Therapy: Different Databases, Different Doses(Başkent Üniversitesi Eczacılık Fakültesi, 2024-03-27) Pehlivanli, Aysel; Yalcin, Tugba Yanik; Yesiler, Fatma Irem; Sahinturk, Helin; Azap, Ozlem Kurt; Zeyneloglu, Pinar; Basgut, BilgenMeticulous antimicrobial management is essential among critically ill patients with acute kidney injury, particularly if renal replacement therapy is needed. Many factors affect drug removal in patients undergoing continuous renal replacement therapy CRRT. In this study, we aimed to compare current databases that are frequently used to adjust CRRT dosages of antimicrobial drugs with the gold standard. The dosage recommendations from various databases for antimicrobial drugs eliminated by CRRT were investigated. The book 'Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys' was chosen as the gold standard. There were variations in the databases. Micromedex, UpToDate, and Sanford had similar rates to the gold standard of 45%, 35%, and 30%, respectively. The Micromedex database shows the most similar results to the gold standard source. In addition, a consensus was reached as a result of the expert panel meetings established to discuss the different antimicrobial dose recommendations of the databases.Item Chymotrypsin and Trypsin Inhibitory Activity of Some Medicinal Plants Collected from Rize (Türkiye)(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-25) Gunbatan, Tugba; Sucu, Melike; Gokbulut, Alper; Dilmac, Elif; Gurbuz, IlhanIn this research, the evaluation of in vitro chymotrypsin and trypsin inhibitory activities of ten plant species collected from Rize were aimed, and fractions that showed strong activity were analyzed through HPLC. Daphne pontica L. and Mentha longifolia (L.) L. were found to have the highest chymotrypsin inhibitory activities (87.75 and 84.24 % inhibition). Similarly, the highest trypsin inhibitory activity was observed in D. pontica (%99.93 inhibition), followed by Sambucus ebulus L. flowers (87.47 % inhibition). Extracts showing strong enzyme inhibition were fractioned and subjected to activity tests. The highest chymotrypsin inhibitory activity was observed in the n-hexane fraction of D. pontica (%80.70 inhibition), while the highest trypsin inhibitory activity was found in the n-butanol fraction of S. ebulus (%86.81 inhibition). HPLC studies determined that the 80 % ethanol extract of D. pontica and its dichloromethane and ethyl acetate fractions contained umbelliferone. It was found that chlorogenic acid was present in the 80 % ethanol extracts of S. ebulus flowers. M. longifolia was found to contain chlorogenic acid, caffeic acid, luteolin-7-glucoside, and rosmarinic acid. M. longifolia has been identified as the plant exhibiting the highest antioxidant activity in ABTS and CUPRAC tests, consistent with its high phenolic and flavonoid content.