Drug metabolism and personalized therapy最新文献

{"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}

{"title":"Application of herbal liniment (<i>'Ṭilā</i>) in the management of pain and disability of chronic migraine: a randomized controlled trial.","authors":"Suresh Kumar Saral, Abdul Nasir Ansari, Mohd Nayab, Khalid Rahim Wani","doi":"10.1515/dmpt-2025-0079","DOIUrl":"10.1515/dmpt-2025-0079","url":null,"abstract":"<p><strong>Objectives: </strong>Chronic migraine is a prevalent and disabling neurological disorder affecting 1-3 % of the global population. Ancient Unani physicians have described herbal liniment (<i>'Ṭilā</i>) as a treatment modality for chronic migraine. This study aimed to evaluate its efficacy in managing the condition.</p><p><strong>Methods: </strong>A randomized controlled trial was conducted on 36 patients with chronic migraine. Participants were divided into two groups: the test group (n=24), which received herbal liniment applied locally once daily for 15 days, and the control group (n=12), which underwent transcutaneous electrical nerve stimulation (TENS) for 30 min daily, 5 days a week, over 2 weeks. Outcomes were measured using the Visual Analogue Scale (VAS), headache frequency, and the Migraine Disability Assessment Scale (MIDAS) on days 15, 30, 60, and 90.</p><p><strong>Results: </strong>Both groups showed significant improvement within the groups in headache frequency (p<0.0001). The test group demonstrated greater effectiveness, with larger reductions in headache frequency (mean difference 39.63; p<0.0001), VAS (mean difference 3.96; p<0.001), and MIDAS (mean difference 2.25; p=0.003).</p><p><strong>Conclusions: </strong>Herbal liniment effectively reduced migraine frequency, intensity, and disability. Larger studies are needed to validate these findings and assess long-term outcomes.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"21-28"},"PeriodicalIF":0.0,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103521","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":"From warfarin resistance to warfarin overdose: an unusual case report.","authors":"Mehmet Uğur Çalışkan","doi":"10.1515/dmpt-2025-0062","DOIUrl":"10.1515/dmpt-2025-0062","url":null,"abstract":"<p><strong>Objectives: </strong>Warfarin resistance represents a rare yet clinically significant challenge, especially among patients with mechanical heart valves. It may result from either hereditary or acquired factors.</p><p><strong>Case presentation: </strong>A 27-year-old male patient with a history of aortic and mitral valve replacement was followed with subtherapeutic International Normalized Ratio (INR) of 1.8-2.0 despite receiving 20 mg/day of warfarin. He was hospitalized for evaluation, and potential acquired causes of warfarin resistance were excluded. The patient was discharged with a plan for close INR monitoring. Following the initiation of lorazepam and olanzapine for a comorbid psychiatric condition, he re-presented with bleeding manifestations due to warfarin overdose. Notably, his apparent warfarin resistance resolved after the addition of these medications, and he has since been maintained within the therapeutic INR range on a stable warfarin dose of 5 mg/day.</p><p><strong>Conclusions: </strong>Warfarin is known to interact with numerous medications, and new drug interactions continue to be reported in the literature. Although no major interactions with lorazepam or olanzapine have been previously documented, in this case the concomitant initiation of these agents appeared to overcome warfarin resistance. This clinical course was remarkable for the apparent resolution of warfarin resistance, raising the possibility of underlying pharmacologic interactions.</p>","PeriodicalId":11332,"journal":{"name":"Drug metabolism and personalized therapy","volume":" ","pages":"51-53"},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040676","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}