Drug metabolism and personalized therapy最新文献

{"title":"MDMA-induced CYP2D6 inhibition: concentration-dependent variability using dextromethorphan as a probe.","authors":"Faezeh Ahmadi, Hoda Lavasani, Mohammadhosein Keshvadi, Youssef Daali, Mohammadreza Rouini, Sanaz Jamshidfar, Yalda H Ardakani","doi":"10.1515/dmpt-2025-0029","DOIUrl":"10.1515/dmpt-2025-0029","url":null,"abstract":"<p><strong>Objectives: </strong>Ecstasy is commonly abused due to entactogenic effects. Although our previous studies on isolated perfused rat model confirmed inhibition of CYP2D6 by MDMA, the time for enzyme recovery was different when mirtazapine and tramadol were used as substrates. Therefore, present study intended to investigate CYP2D6 inhibition by MDMA using dextromethorphan as a well-known probe. Two different concentrations of dextromethorphan were used at therapeutic and saturated level to clarify observations.</p><p><strong>Methods: </strong>Thirty-two rats were divided into two groups (dextromethorphan concentration: 2 µM or 300 µM). Each group was divided into four subgroups. Except for control, three treatment subgroups received a single dose of MDMA (1 mg/kg) 1 h, 1 week, and 1 month before liver perfusion, respectively.</p><p><strong>Results: </strong>Mean metabolic ratio using therapeutic dextromethorphan concentration showed a statistically significant decrease only in the 1-hour group compared to control. The results of the mean metabolic ratio using the saturated concentration showed a reduction in all treatment groups (p-value<0.05).</p><p><strong>Conclusions: </strong>It can be concluded that the isoenzyme behavior can be completely different using therapeutic vs. saturated probe concentrations. The best explanation for the duality observed in metabolic behavior seems to be the dependence of the metabolite on enzymatic pathway.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"103-108"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257732","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":"Allergic reactions to anaesthetics in surgery: current challenges and perspectives.","authors":"Maria Zofia Lisiecka, Joanna Luczak","doi":"10.1515/dmpt-2026-0008","DOIUrl":"10.1515/dmpt-2026-0008","url":null,"abstract":"<p><strong>Introduction: </strong>This study was conducted to assess the current state of issues related to AR to anaesthetics used in surgical procedures.</p><p><strong>Contents: </strong>A literature review of scientific publications in allergology and anaesthesiology was performed, evaluating the allergenic profile of modern anaesthetics and analysing approaches to preventing AR during surgery.</p><p><strong>Summary: </strong>Currently, the most commonly used local anaesthetics are amides, including lidocaine, bupivacaine, articaine, mepivacaine, ropivacaine, and levobupivacaine. These are considered safer in terms of allergenicity compared to their ester-based predecessors - novocaine, benzocaine, and tetracaine - as their metabolites rarely act as allergens. Among general anaesthetics, intravenous agents such as propofol, midazolam, etomidate, and ketamine, as well as inhalational agents including sevoflurane, isoflurane, desflurane, and xenon, are widely used. These are generally safer than their predecessor, thiopental, with xenon currently exhibiting the highest safety profile due to its inert chemical properties. Muscle relaxants have the highest allergenic potential, as their mechanism of action - blocking acetylcholine receptors - can lead to cell damage and the release of immune-stimulating substances. The only representative of depolarising muscle relaxants is succinylcholine, while non-depolarising agents include atracurium, cisatracurium, vecuronium, rocuronium, pancuronium, and mivacurium.</p><p><strong>Outlook: </strong>Preventive measures to reduce the risk of AR include: a detailed patient history and diagnostic testing using skin tests, provocation tests, and/or blood tests for immunoglobulin E (IgE); replacement of the allergenic drug with a safer alternative if an allergy is confirmed; close monitoring for allergic manifestations during surgery, with professional preparedness for resuscitation in cases of anaphylaxis; postoperative patient monitoring to detect potential delayed AR; documentation of all AR for future reference. The findings of this study may be applied in clinical practice to mitigate the risks of AR associated with anaesthetic use during surgical interventions.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"125-135"},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148149077","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":"Superior seizure control with first-line levetiracetam in very low birth weight neonates: a 10-year comparative retrospective study.","authors":"Coşkun Armağan, Begüm Nişancı Öğünçlü, Mustafa Halk, Uluç Yiş, Ayşe Semra Hız Kurul, Funda Erdoğan, Nuray Duman, Hasan Özkan","doi":"10.1515/dmpt-2026-0011","DOIUrl":"10.1515/dmpt-2026-0011","url":null,"abstract":"<p><strong>Objectives: </strong>Very low birth weight (VLBW) infants are at disproportionately high risk for neonatal seizures, yet optimal first-line antiseizure medication (ASM) strategies in this vulnerable population remain a matter of debate. Over the past decade, levetiracetam (LEV) has emerged as a promising alternative to phenobarbital (PB), driven by growing concerns over PB's limited efficacy and potential neurotoxic effects.</p><p><strong>Methods: </strong>This retrospective cohort study analyzed medical records of VLBW infants treated for seizures at our Neonatal Intensive Care Unit from 2013 to 2023. We compared the efficacy and safety of LEV and PB as initial antiepileptic treatments. Data on gestational age, birth weight, type of seizures, electroencephalogram findings, and treatment outcomes were meticulously collected and analyzed.</p><p><strong>Results: </strong>The study included 103 VLBW infants (mean gestational age 26.17±2.31 weeks); 27 received LEV and 76 received PB. Baseline demographic and clinical characteristics were comparable between the two groups. Although the LEV group had a higher proportion of infants with severe intraventricular hemorrhage and necrotizing enterocolitis indicating a potentially more critical baseline, these differences were not statistically significant. The primary outcome revealed that significantly fewer infants in the LEV group were unresponsive to initial treatment compared to the PB group (14.8 vs. 56.6 %; p<0.001). Furthermore, lower gestational age was identified as a significant risk factor for PB unresponsiveness.</p><p><strong>Conclusions: </strong>This study supports that LEV is more successful in clinical seizure control compared to PB as the first choice in ASM selection in VLBW. If our study results are supported by randomized controlled prospective studies, LEV, with its potentially fewer side effects, could be included in clinical algorithms as the first-choice ASM especially for VLBW.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"109-117"},"PeriodicalIF":0.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040901","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":"Allele frequencies of pharmacogenetic biomarkers and genomic ancestry in a sample of the Cuban population.","authors":"Hilda Roblejo-Balbuena, Yaima Zuñiga-Rosales, Goitybell Martínez-Téllez, Claudia Alemañy Díaz-Perera, Giselle Monzón-Benítez, Jonas Bybjerg-Grauholm, Ole Mors, Beatriz Marcheco-Teruel","doi":"10.1515/dmpt-2025-0038","DOIUrl":"10.1515/dmpt-2025-0038","url":null,"abstract":"<p><strong>Objectives: </strong>A growing set of drugs includes a pharmacogenetic biomarker as a requirement before prescription. This study aims to determine the frequency of allelic variants with functional repercussions in clinically relevant pharmacogenes and its relation with genomic ancestry in Cuban individuals.</p><p><strong>Methods: </strong>10 single nucleotide variants (SNVs) across eight genes, included in the list of genetic variants required for the prescription of warfarin, tacrolimus, azathioprine, simvastatin, carbamazepine, abacavir and clopidogrel were analyzed. From genotyping in 948 Cuban individuals, population frequencies and Hardy-Weinberg equilibrium assessment were determined using PLINK v1.9. As a result of the ADMIXTURE analysis, previously performed on this sample, the relationship with the individual proportion of contribution of European, African, Native American and Asian ancestry was evaluated.</p><p><strong>Results: </strong>Minor allele frequencies (MAFs) ranged from 0.0216 to 0.2781. Hardy-Weinberg equilibrium (HWE) deviations in three variants (<i>CYP2C9</i> rs1799853, <i>HLA-A</i> rs1061235<i>, SLCO1B1</i> rs4149056) were identified. Among individuals presenting the SNVs <i>CYP2C9</i> rs1799853, <i>CYP4F2</i> rs2108622, <i>SLCO1B1</i> rs4149056, <i>HLA-B</i> rs2395029, the average European ancestry was higher; in contrast, individuals with the variant <i>CYP3A5</i> rs10264272 presented higher African ancestry.</p><p><strong>Conclusions: </strong>The variability in the analysis of each included allele, is representative of the genetic heterogeneity of the Cuban population and provides a remarkable example of diversity among populations.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"93-101"},"PeriodicalIF":0.0,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971152","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":"The 10+2 Santorini Conference: Systems Medicine and Personalised Health Therapy. The Odyssey from Hope to Practice: \"Patient First - <i>Keep Ithaca always in your mind</i>\" Santorini, Greece, 26-29 May 2026.","authors":"Sofia Siest","doi":"10.1515/dmpt-2026-0005","DOIUrl":"10.1515/dmpt-2026-0005","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"55-57"},"PeriodicalIF":0.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765568","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":"<i>Drug metabolism and personalized therapy</i> is switching its publication model to open access.","authors":"Suzanne Mekking, Ingrid Fricke-Galindo, Adrián LLerena","doi":"10.1515/dmpt-2026-0010","DOIUrl":"10.1515/dmpt-2026-0010","url":null,"abstract":"","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644347","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":"Regulatory discrepancies and patient-safety risks from the continued marketing of withdrawn medicines in Ecuador, Colombia, and Peru (2014-2025).","authors":"Aida Miranda, Camila Lopez, Shabnam Santos, Ariel Moncayo, Fatima Morales, Enrique Teran","doi":"10.1515/dmpt-2025-0081","DOIUrl":"10.1515/dmpt-2025-0081","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate whether international decisions to withdraw medicines for safety, efficacy, or commercial reasons were reflected in the regulatory actions of Ecuador, Colombia, and Peru.</p><p><strong>Methods: </strong>A retrospective, descriptive, cross-sectional analysis identified active pharmaceutical ingredients (APIs) withdrawn globally by Stringent Regulatory Authorities (SRAs) between January 1, 2014, and June 30, 2025. Data were obtained from published SRA communications and verified in national regulatory databases - ARCSA (Ecuador), INVIMA (Colombia), and DIGEMID (Peru) - to determine current marketing status. APIs were categorized as <i>never registered</i> (no evidence in current or archival databases), <i>previously registered</i> (formally canceled/suspended with a safe of efficacy rationale), <i>previously registered</i> (authorization expired without an explicit safety rationale), or <i>currently registered</i> (active marketing authorization).</p><p><strong>Results: </strong>Fifty-three APIs were withdrawn internationally, predominantly for safety concerns (69.81 %), followed by lack of efficacy (22.64 %) and manufacturer decisions (7.55 %). The European Medicines Agency issued most withdrawals, particularly for oncologic and hormonal agents. Despite these actions, Ecuador retained 16.98 % of withdrawn APIs on its market, Peru 7.55 %, and Colombia 7.55 %. Persisting products included modified-release paracetamol, hydroxyethyl starch, and ulipristal 5 mg - drugs associated with hepatotoxicity or fatal adverse events. Regulatory databases often list expired or active authorizations without public withdrawal notices.</p><p><strong>Conclusions: </strong>Substantial misalignment persists between international and Andean regulatory decisions. The continued regulatory authorization of withdrawn medicines highlights weaknesses in pharmacovigilance and transparency, underscoring the urgent need for regional harmonization and public disclosure of regulatory actions.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"85-91"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456396","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":"The molecular landscape of kidney stone disease: pathophysiology to personalized intervention.","authors":"Neha Sharma, Joy Das, Utpal Bhui, Biplab Debnath, Mohini Mondal, Rajarshi Nath, Nallapuraju Jahnavi, Shreya Chowdhury, Yogesh Shinde, Navneet Khurana, Bimlesh Kumar, Md Sadique Hussain, Sathvik Belagodu Sridhar, Uttam Prasad Panigrahy, Sumel Ashique, Priya Chaudhary, Mohammad Yousuf Ansari","doi":"10.1515/dmpt-2025-0083","DOIUrl":"10.1515/dmpt-2025-0083","url":null,"abstract":"<p><p>Urolithiasis is a complex and multifactorial disease with rising global prevalence. Traditional management strategies primarily focus on symptom relief and surgical intervention. However, with advances in genomics, metabolomics, and imaging technologies, precision medicine is reshaping the diagnostic and therapeutic landscape of kidney stone diseases. This review explored the integration of genetic screening, individualized metabolic evaluation, and risk stratification to enable tailored treatment plans. We discuss the current and emerging approaches that align with the principles of precision medicine, including the identification of monogenic and polygenic risk factors, advanced imaging for stone composition, and targeted lifestyle or pharmacological interventions. These developments herald a paradigm shift in urolithiasis care, moving beyond reactive treatment toward proactive, patient-specific management.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"59-83"},"PeriodicalIF":0.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316179","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":"CYP2C19 genetic polymorphisms and proton pump inhibitor therapy resistance in patients with gastrooesophageal reflux disease: a preliminary observational cohort study.","authors":"Jamie-Lee DeBattista, Graziella Zahra, Christopher Barbara, John Schembri, Lilian M Azzopardi, Francesca Wirth","doi":"10.1515/dmpt-2025-0077","DOIUrl":"10.1515/dmpt-2025-0077","url":null,"abstract":"<p><strong>Objectives: </strong>Clinical relevance of CYP2C19 genetic polymorphisms in real-world patient populations requires further investigation. This study aimed to determine the prevalence of CYP2C19 genetic variants in patients with GORD showing resistance to PPI therapy and possible clinical implications.</p><p><strong>Methods: </strong>Patients with GORD and documented PPI resistance were identified from ambulatory reflux monitoring and endoscopy databases. EDTA blood samples were obtained for CYP2C19 genotyping using real-time polymerase chain reaction and reverse hybridisation. Genotypes (phenotypes) were categorised into: <i>*1/*1</i> (normal metabolisers, NMs), <i>*1/*17</i> (rapid metabolisers, RMs), <i>*17/*17</i> (ultra-rapid metabolisers, UMs), <i>*1/*2, *2/*17</i> (intermediate metabolisers, IMs), <i>*2/*2</i> (poor metabolisers, PMs).</p><p><strong>Results: </strong>Fifty patients were assessed (49 European ancestry, 28 male, modal age 50-59 years). Predominant resistance patterns included reflux hypersensitivity (n=19) and persistent oesophagitis (n=17). PPI therapy included esomeprazole (n=26), omeprazole (n=22), lansoprazole (n=2). Genotyping identified 26 NMs (52 %), 8 RMs (16 %), 14 IMs (28 %), 2 PMs (4 %); no UMs were identified.</p><p><strong>Conclusions: </strong>Findings from this preliminary study indicate a higher frequency of NMs and RMs compared to IMs and PMs in this PPI-resistant cohort with GORD. Most resistance was observed to the second-generation PPI esomeprazole. A limitation was the lack of a control group comprising PPI-sensitive patients.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"29-37"},"PeriodicalIF":0.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321486","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":"Allergy to muscle relaxants: diagnosis and significance of drug concentrations.","authors":"Maria Zofia Lisiecka","doi":"10.1515/dmpt-2025-0066","DOIUrl":"10.1515/dmpt-2025-0066","url":null,"abstract":"<p><strong>Objectives: </strong>Allergic reactions to muscle relaxants are a major cause of perioperative anaphylaxis. This study aimed to evaluate how plasma concentrations of muscle relaxants, genetic predispositions, and immunometabolic changes influence the risk and severity of hypersensitivity reactions to improve diagnostic accuracy and support personalised perioperative management.</p><p><strong>Methods: </strong>A total of 120 adult patients undergoing general anaesthesia were examined using intradermal testing, ELISA-based assays for specific IgE, basophil activation tests, cytokine profiling, plasma drug concentration measurements (HPLC-MS), molecular genetic analysis of IL-4 and IL-13 polymorphisms, and proton magnetic resonance spectroscopy for metabolic profiling. A control group (n=60) underwent parallel testing. Statistical evaluation included correlation analysis, logistic regression, and ROC curve assessment.</p><p><strong>Results: </strong>Positive allergic reactions were observed in 15.8 % of patients, most commonly to atracurium (9.2 %). Patients with positive reactions showed significantly higher plasma concentrations of atracurium (2.8 ± 0.4 μg/mL vs. 1.7 ± 0.3 μg/mL; p<0.01). <i>IL-4</i> (CC) and <i>IL-13</i> (AA) genotypes increased the risk of hypersensitivity (OR 3.2 and 2.8, respectively), while their combination markedly elevated the likelihood of severe reactions (OR 5.6). Elevated <i>IL-4</i>, <i>IL-6</i>, and <i>TNF-α</i> levels correlated with clinical severity. Metabolic profiling revealed increased lactate, acetate, and pyruvate in allergic patients, indicating systemic inflammatory and anaerobic metabolic responses. ROC analysis confirmed high predictive accuracy for atracurium concentration (AUC=0.82) and genetic markers (AUC=0.79).</p><p><strong>Conclusions: </strong>Allergic reactions to muscle relaxants are strongly influenced by drug concentration, genetic susceptibility, and metabolic responses. Combined pharmacokinetic, immunological, and genetic assessment may significantly enhance preoperative risk stratification and support personalised anaesthetic management to improve patient safety.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"39-50"},"PeriodicalIF":0.0,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321512","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}