Drug metabolism and bioanalysis最新文献

{"title":"The Pharmacokinetic and Pharmacodynamic Drug-drug Interaction Potential of Cannabidiol.","authors":"Guillermo Alberto Keller, Jorge Alejandro Aimar","doi":"10.2174/0118723128411684251029100517","DOIUrl":"https://doi.org/10.2174/0118723128411684251029100517","url":null,"abstract":"<p><p>Although Cannabidiol (CBD) has recently been approved for use in some neurological diseases, the pharmacology of CBD is not fully understood. Experimental reports suggest CBD inhibits a large number of enzymes, generating the possibility of multiple interactions. The aim is to describe the main known interactions, evidence, and actual risk in clinical practice. Existing indexed publications and product monographs were reviewed. The authors cataloged and classified the information based on the severity of the interaction, type (Pharmacokinetic vs. Pharmacodynamic), and level of evidence. 1,289 drug-drug interactions were identified (634 pharmacokinetic and 655 pharmacodynamic interactions). There were a total of 19 major interactions (colchicine, levomethadyl acetate, Mipomersen, propoxyphene, brexanolone, buprenorphine, esketamine, fezolinetant, ketamine, leflunomide, levoketoconazole, lomitapide, morphine, pexidartinib, pralsetinib, relugolix, sodium oxybate, teriflunomide, venetoclax), 393 moderate interactions, 49 minor interactions, and 828 of unknown significance. Drugs that should be avoided in the presence of cannabidiol, those that should be monitored, and those interactions that, while frequently mentioned, do not present sufficient evidence to recommend therapeutic changes are identified. The information highlights the need for caution. While many interactions have been postulated, only a small group warrants consideration in clinical practice. For the remaining drugs, special caution is needed. The long history of human use of the cannabis plant is often confused with the limited timeframe for scientific study of its isolated derivatives. The available information allows us to identify drugs with potential Drug-Drug Interactions of varying severity. This information can be used to improve treatment safety.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 2","pages":"107-118"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Therapeutic Strategies in Targeting Alpha Synuclein Dysfunction Pathways for Parkinson's Disease Treatment.","authors":"Kranthi Kumar Guduru, Ravi Gundawar, Bhargav Eranti, Kavya Turaga, Sahista Anjum S, Pavithra Tadimarri, Hari Priya Pujari, Waseem Taj Mahasool, Padma Priya Arigela","doi":"10.2174/0118723128397400250910222116","DOIUrl":"https://doi.org/10.2174/0118723128397400250910222116","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative, progressive disorder presenting with both motor and non-motor symptoms. Its pathogenesis likely results from dysfunction of the presynaptic protein alpha-synuclein, which produces neuronal toxicity and aggregation in Lewy bodies. Relevant literature was identified through systematic searches in PubMed, Scopus, Web of Science, and Google Scholar using a range of descriptors in English. In this review, we investigated novel therapeutic strategies targeting alpha-synuclein, including small molecule inhibitors, immunotherapies, RNA-based therapies, and protein clearance mechanisms. It also reviews our recent advances in nanotechnological development for drug delivery systems to enhance therapeutic efficacy using lipid- based nanoparticles, polymeric carriers, and exosome delivery. Although much progress has been achieved, including clinical translation, biomarker development, and large-scale production, many challenges still remain. With the help of emerging trends such as AI-driven nanotechnology and personalized medicine, these gaps can be targeted. We emphasize the importance of integrated and multi-targeted approaches for the development of effective disease-modifying therapies for PD.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 2","pages":"95-106"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics Methods for Detecting Acetaminophen Poisoning: A Systematic Review.","authors":"Tamilarasan Murugesan, Hemasri Velmurugan","doi":"10.2174/0118723128399568250908093801","DOIUrl":"10.2174/0118723128399568250908093801","url":null,"abstract":"<p><strong>Introduction: </strong>Detecting toxicity patterns in metabolic changes is a key indicator of potential threats. Metabolomics may provide an alternative way to find biomarkers for drug overdose and toxicity. In an acetaminophen overdose, glutathione scavenging causes mitochondrial malfunction and hepatocyte death. Metabolomics methods have enabled the discovery of novel mechanisms of liver injury in acetaminophen (APAP) overdose.</p><p><strong>Methods: </strong>We conducted a peer-reviewed scientific review to assess the studies on the application of metabolomics in APAP poisoning. We searched PubMed and Scopus databases until February 28, 2025, for relevant original articles. We also looked into the clinicaltrials.gov website and the Indian clinical trial registry.</p><p><strong>Results: </strong>Our initial search yielded 302 articles, after duplicates and initial screening. Two hundred and nine (209) articles underwent full-text review. Of these, 191 articles were excluded, and 18 studies were included. There were 1503 subjects, and 24 metabolomics techniques were used. Seven trials were registered in clinicaltrials.gov, and none were registered in the CTRI.</p><p><strong>Discussion: </strong>Metabolic intermediates are more likely to pass through intact cell membranes and be detected in blood before cell death. Thus, metabolomics could be a potential strategy to identify damage biomarkers relevant at earlier periods.</p><p><strong>Conclusion: </strong>APAP can be considered a multifunctional drug with significantly fewer adverse effects; however, it still affects the liver when used chronically. Scientists continue to push the boundaries of data extraction, and it is widely acknowledged that a lack of tools for data integration hampers the full manifestation of metabolomics technologies. This research increases our understanding of metabolomics use in APAP-induced liver injury.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 2","pages":"143-155"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149130269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the Forced Degradation Behaviour of Oteseconazole and Characterization of Its Degradants by LC-MS/MS.","authors":"Meera Devi Mazhavancheril, K G Baheti","doi":"10.2174/0118723128392142250630064916","DOIUrl":"https://doi.org/10.2174/0118723128392142250630064916","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Oteseconazole is a novel tetrazole antifungal agent used to treat recurrent Vulvovaginal Candidiasis in women. Its mechanism of action is through the inhibition of cytochrome P450(CYP)51, thereby affecting the development and integrity of the fungal cell membrane. The main objective of the present work is to investigate the forced degradation behaviour of Oteseconazole, identify its degradants, and propose the fragmentation pathways of the degradants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Good chromatographic separation of Oteseconazole was achieved using an HPLC System equipped with a PDA detector, and an X-Bridge Phenyl column (150 x 4.6mm, 5μm) with a mobile phase comprising acetonitrile and trifluoroacetic acid buffer (50:50) run in isocratic mode at 268 nm. For mass analysis, the HPLC system was connected to a SCIEX QTRAP 5500 mass spectrometer, operated in positive ion electrospray ionization interface mode.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;An accurate, specific, and time-efficient stability-indicating RP-HPLC method was developed for the estimation of Oteseconazole and its degradation products. The developed method was validated with Linearity in a range of 1.25μg/ mL - 7.5 μg/mL, accuracy (%RSD 0.06), system precision (%RSD 0.256), method precision (% RSD 0.49), LOD(0.3μg/mL), and LOQ(1μg/mL). Upon forced degradation studies according to ICH guidelines, Oteseconazole was found to be stable in photolytic, hydrolytic, and thermal conditions but degraded readily in acidic, alkaline, peroxide, and reduction environments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The developed method was robust and can be used in routine analysis to quantify Oteseconazole. The degradation behaviour of Oteseconazole was studied by performing forced degradation studies according to the ICH guidelines, and it was found to be stable in photolytic, hydrolytic, and thermal conditions, but degraded more readily in acidic, alkaline, peroxide, and reductive environments. The degradation products were characterized by LC-MS/MS, and their fragmentation pathways were proposed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Oteseconazole remained stable in photolytic, hydrolytic, and thermal conditions, but showed significant degradation in acidic, alkaline, peroxide, and reductive environments. The degradation products were characterized by LC-MS/MS and characterized as 5-(4-chlorophenyl)-2-(2- (2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propyl)pyridine (acid impurity, DP1), sodium 4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)phenolate (alkali impurity, DP2), 2-(2-(2,4-difluorophenyl)-1,1-difluroropropyl)-5-(4-hydroperoxyphenyl)pyridine (peroxide impurity, DP3) and 4-(6-2(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1- yl)propyl)pyridin-3-yl)phenyl hydrogen sulfate (reduction impurity, DP4), and their fragmentation pathways were proposed. The developed method was accurate, specific, less time-consuming, a","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 1","pages":"51-67"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP3A4-mediated Effects of Cranberry and Pomegranate Juices on Alprazolam Pharmacodynamics.","authors":"Sunil Kumar Kadiri, K N Kotresh, Darshan Gowda Bharathi Srinivasa, K B Premakumari, Prashant Tiwari, B Ramanagowda, Merugumolu Vijay Kumar","doi":"10.2174/0118723128388875250701100724","DOIUrl":"https://doi.org/10.2174/0118723128388875250701100724","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Alprazolam, a frequently prescribed anxiolytic, is extensively metabolized in the liver mostly by the cytochrome P450 3A4 (CYP3A4) enzyme. Cranberry and pomegranate juices, often suggested for their possible therapeutic effects in kidney stone management, have been identified as strong inhibitors of CYP3A4. This raises considerable concerns about possible drug-food interactions that could modify the pharmacodynamic profile of alprazolam. This study aimed to comprehensively assess the pharmacodynamic interactions between alprazolam and these juices, focusing on their collective impact on behavioral and histological results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Molecular docking studies were conducted utilizing AutoDock Vina to assess the binding affinities of active compounds from cranberry and pomegranate juices to the CYP3A4 enzyme, resulting in binding energies of -9.2 and -9.3 kcal/mol, respectively. In vivo tests were performed on adult male Wistar albino rats, which were divided into five experimental groups: control, alprazolam alone, and alprazolam co-administered with cranberry juice, pomegranate juice, or a combination of both. Pharmacodynamic interactions were evaluated via behavioral analyses using the Elevated Plus Maze, Rotarod, and Y-Maze tests to assess anxiety, motor coordination, and cognitive performance. Furthermore, histological analyses of brain tissues were performed to detect neuronal changes and evaluate the degree of neurodegeneration linked to the treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Molecular docking analyses revealed strong binding affinities of anthocyanins from cranberries and ellagic acid from pomegranates to the CYP3A4 enzyme, suggesting their ability to inhibit its activity. Behavioral tests indicated considerable deficits in memory and motor coordination in groups receiving cranberry or pomegranate drinks in conjunction with alprazolam, relative to the alprazolam-only and control groups. Histopathological examination of brain tissues supported these findings, revealing a significant elevation in neuronal degeneration in the coadministration groups compared to controls, indicating a synergistic effect on neurotoxicity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;The pharmacodynamic changes observed suggest that the coadministration of cranberry and pomegranate juices with alprazolam alters the drug's effects, likely due to CYP3A4 inhibition by the juices' phytochemicals. These interactions may enhance alprazolam's neuropharmacological effects, resulting in an increased risk of cognitive and motor impairments. These findings underscore the clinical importance of monitoring food-drug interactions, especially in patients using natural products concurrently with CNS-active medications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study highlights significant pharmacodynamic interactions between alprazolam and cranberry/pomegranate juices, highlighting their potential to influence the drug's therap","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 1","pages":"68-78"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Profile Evaluation of Narrow Therapeutic Index Drugs in Tertiary Care Teaching Hospital.","authors":"G Lakshmi Narasimha, N Lathapriya, D Girirajasekhar, P Rajitha, P Kalpana, K Leela Prasad, C Durga Prasad","doi":"10.2174/0118723128375801250907163935","DOIUrl":"10.2174/0118723128375801250907163935","url":null,"abstract":"<p><strong>Introduction: </strong>Narrow therapeutic index (NTI) drugs have a small margin between effective and toxic doses, so minor changes in blood levels can cause therapeutic failure or toxicity, leading to significant drug-related problems. The study aims to assess drug-related problems (DRPs) linked to NTI drugs at Government General Hospital, Kadapa, by screening prescriptions, classifying DRPs using Pharmaceutical Care Network Europe (PCNE) v9.0, implementing interventions to reduce them, and calculating drug risk ratios to determine each drug's contribution.</p><p><strong>Methods: </strong>A six-month prospective observational study (June-November 2023) included 110 inpatients prescribed at least one NTI drug. Data from standardized forms and hospital records were analyzed, with DRPs identified using PCNE v9.0, Micromedex, and WHO adverse drug reaction (ADR) scales.</p><p><strong>Results: </strong>Of 110 patients, 48 (43.6%) had DRPs, mainly males (60.4%) aged 31-60 years. Treatment effectiveness issues dominated (74.5%), with major interactions from digoxin, telmisartan, and heparin. Heparin showed the highest drug risk ratio (0.53), indicating significant safety concerns.</p><p><strong>Discussion: </strong>Findings highlight the high DRP risk from multiple NTI drug prescriptions, particularly heparin and digoxin. Results align with existing research and underscore the role of clinical pharmacy in DRP prevention. Drug risk ratio offers a quantitative tool for prioritizing monitoring.</p><p><strong>Conclusion: </strong>In our study, the most common DRPs observed were related to the drug use process. Heparin and digoxin were found to be high-risk drugs, according to study results. Hence, special observation and monitoring from physicians and other health professionals are needed for the prescriptions with NTI drugs.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 2","pages":"191-201"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Impacts of Clinically Effective Antihypertensive Herbal Medicines on the Activities of Major Drug Metabolizing Enzymes and Transport Proteins.","authors":"Sharon Iyobor Igbinoba, Cyprian Ogbonna Onyeji, Adebanjo Jonathan Adegbola, Adebusuyi Akande Ademisoye, Julius Olugbenga Soyinka","doi":"10.2174/0118723128380660250717140750","DOIUrl":"https://doi.org/10.2174/0118723128380660250717140750","url":null,"abstract":"<p><strong>Introduction: </strong>Hypertension is one of the most common non-communicable diseases, and reports indicate that its prevalence is escalating globally due to several factors. Studies in different countries have shown an upsurge in the use of Herbal Medicinal Products (HMPs), including herbal antihypertensive medicines taken by people with hypertension, and 20-80 % of hypertensive patients concurrently use these herbal medicines and conventional antihypertensive medicines or other drugs. The safety and efficacy of the concurrent use of herbal and orthodox medicines are of great concern because of the high possibility of herb-drug interactions.</p><p><strong>Methods: </strong>An extensive literature search was undertaken, and the information obtained was subjected to critical analysis. This review aimed to update the available data on HMPs with reproducible evidence-based antihypertensive efficacies. Additionally, the major phytochemical and bioactive constituents of these HMPs were identified along with a discussion of their potential to modulate activities of drug-metabolizing enzymes and drug transport systems, especially Pglycoprotein.</p><p><strong>Results: </strong>More than 50 commonly used medicinal plants from different regions of the world have been documented for their anti-hypertensive activity. Most of these studies used animal models to authenticate the antihypertensive activities of the herbs. In contrast, a few studies on extracts of Hibiscus sabdariffa, Allium sativum, Apium graveolens, Nigella sativa, Linum usitatissimum, and Camellia sinensis involved clinical trials. Potentials for herb-drug interactions varied among the clinically effective HMPs due to the wide variability in their phytochemical constituents.</p><p><strong>Conclusion: </strong>Safety issues in using these HMPs were highlighted by the identification of beneficial or adverse, clinically significant herb-drug interactions.</p>","PeriodicalId":521353,"journal":{"name":"Drug metabolism and bioanalysis","volume":"19 1","pages":"1-28"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}