Expert opinion on drug metabolism & toxicology最新文献

Evaluating the drug interactions in kratom Usage: clinical application. 评价克拉通用药中的药物相互作用：临床应用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-16 DOI: 10.1080/17425255.2025.2521045

Leena R Dhoble, Abhishek Gour, Christopher R McCurdy, Abhisheak Sharma

{"title":"Evaluating the drug interactions in kratom Usage: clinical application.","authors":"Leena R Dhoble, Abhishek Gour, Christopher R McCurdy, Abhisheak Sharma","doi":"10.1080/17425255.2025.2521045","DOIUrl":"https://doi.org/10.1080/17425255.2025.2521045","url":null,"abstract":"Mitragyna speciosa: (Korth.) Havil. (Rubiaceae), commonly known as kratom, is a tropical tree native to Southeast Asia, traditionally used for its diverse ethnopharmacological activities, including analgesic and anxiolytic effects. Kratom's unique pharmacological profile allows it to function as a stimulant at low doses and produces opioid-like effects at high doses, making it a potential alternative for pain management and mitigation of opioid use disorder.Areas covered: Google scholar and PubMed, along with FAERS database, were systematically searched to evaluate the clinical applications of kratom by examining its drug interactions, which can significantly impact the pharmacokinetics and pharmacodynamics of concomitant medications. By examining current evidence, this review aims to highlight the importance of establishing safe clinical practices and protocols for healthcare providers and patients.Expert opinion: Evaluating drug interactions in kratom usage is clinically imperative because kratom's bioactive alkaloids can interact with the pharmacokinetic and pharmacodynamic processes of concurrent medications, potentially resulting in adverse effects or compromised therapeutic outcomes. This review presents an expert opinion on the clinical relevance of kratom's interactions with drugs, aiming to inform clinical practice, highlight ethical and regulatory considerations, and propose future research directions to improve the understanding of kratom's pharmacological profile and enhance user safety.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304092","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}

引用次数: 0

The effect of prolonged treatment with antipsychotic drugs on cytochrome P450 - drug metabolizing enzymes. Mechanisms of action and significance for pharmacotherapy. 抗精神病药物长期治疗对细胞色素P450 -药物代谢酶的影响。作用机制及其对药物治疗的意义。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-13 DOI: 10.1080/17425255.2025.2517731

Agnieszka Basińska-Ziobroń, Przemysław Jan Danek, Władysława Anna Daniel

{"title":"The effect of prolonged treatment with antipsychotic drugs on cytochrome P450 - drug metabolizing enzymes. Mechanisms of action and significance for pharmacotherapy.","authors":"Agnieszka Basińska-Ziobroń, Przemysław Jan Danek, Władysława Anna Daniel","doi":"10.1080/17425255.2025.2517731","DOIUrl":"10.1080/17425255.2025.2517731","url":null,"abstract":"Introduction: The treatment of schizophrenia and other psychosis-related mental disorders requires long-term therapy with selected drugs possessing adequate pharmacological receptor spectra, relevant to the patient's clinical state. Antipsychotics can interact with cytochrome P450 (CYP) reciprocally affecting each other in different ways. The enzyme plays an important role in the metabolism of antipsychotics, whereas antipsychotics can affect CYP enzymes in the liver and brain.Areas covered: The effects of short and prolonged administration of antipsychotic drugs belonging to different groups (first-, second- and third-generation) on the expression and activity of CYP enzymes in the liver and brain are presented (based on PubMed 3 December 2024). Possible relations between pharmacological receptor spectra of antipsychotics and their influence on the regulation of cytochrome P450 in the liver and brain are considered. The results are discussed in the light of pharmacological and therapeutic significance.Expert opinion: During continuous treatment in vivo, the direct mechanisms (drug/metabolite binding to the CYP enzyme) overlap with the effect of antipsychotics on CYP regulation (enzyme induction or inhibition). Clinicians using the information on particular drug-CYP interaction in combination with pharmacogenetic data can make informed decisions about drug selection and dosage, ultimately advancing more effective and safer pharmacotherapy.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259681","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}

引用次数: 0

Comparison of ADMET profile between thiosemicarbazide and semicarbazide derivatives regarding anticancer properties. 硫代氨基脲与氨基脲衍生物抗癌性能的ADMET谱比较。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-13 DOI: 10.1080/17425255.2025.2520561

Łucja Justyna Walczak, Mariola Herbet

{"title":"Comparison of ADMET profile between thiosemicarbazide and semicarbazide derivatives regarding anticancer properties.","authors":"Łucja Justyna Walczak, Mariola Herbet","doi":"10.1080/17425255.2025.2520561","DOIUrl":"https://doi.org/10.1080/17425255.2025.2520561","url":null,"abstract":"Introduction: The incidence of cancer is constantly increasing, and current cytostatics are not effective enough and cause serious side effects. Thio/semicarbazide derivatives seem to be promising candidates for anticancer drugs. This systematic review aimed to analyze comparatively the ADMET profiles of thiosemicarbazides and semicarbazides with proven antitumor activity published through August 2024.Methods: A search of PubMed, ScienceDirect and Google Scholar databases was performed. Qualified compounds were subjected to in silico analysis using ADMETlab 2.0 software. The data were statistically analyzed (Student's t-test, Mann-Whitney U test, Chi2).Results: Comparative analysis showed that semicarbazides have more favorable intestinal absorption properties and lower biological activity but have higher selectivity of action and lower risk of drug interactions. Thiosemicarbazides have a higher probability of metabolic activity with concomitant increased toxicity. These compounds show significantly higher levels of binding to plasma proteins, a lower average percentage of the unbound fraction, and a longer half-life.Conclusions: In light of anticancer therapies, thiosemicarbazides can cause increased oxidative stress and DNA damage, which is one strategy for cancer treatment. However, semicarbazides are better candidates for anticancer drug trials because of their better pharmacokinetic and pharmacodynamic profiles and lower toxicity.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287648","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}

引用次数: 0

Mechanism-based drug safety testing using innovative in vitro liver models: from DILI prediction to idiosyncratic DILI liability assessment. 基于机制的药物安全性测试使用创新的体外肝脏模型：从DILI预测到特异性DILI责任评估。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-11 DOI: 10.1080/17425255.2025.2516051

Sibel Bahtiri, Tessa M S Hagens, Bob van de Water, Marije Niemeijer

{"title":"Mechanism-based drug safety testing using innovative in vitro liver models: from DILI prediction to idiosyncratic DILI liability assessment.","authors":"Sibel Bahtiri, Tessa M S Hagens, Bob van de Water, Marije Niemeijer","doi":"10.1080/17425255.2025.2516051","DOIUrl":"10.1080/17425255.2025.2516051","url":null,"abstract":"Introduction: Idiosyncratic drug-induced liver injury (iDILI) remains unpredictable. As adverse responses arise in a small fraction of patients, drugs often fail in later drug development stages or post-approval, thereby tremendously increasing costs and putting patients at risk, highlighting the need for accurate early identification of iDILI liabilities.Covered areas: Using articles from the last 5 years (PubMed), iDILI risk factors are described, in vitro liver models and mechanism-based readout strategies are evaluated on their potential to enable iDILI liability assessment.Expert opinion: Various in vitro liver models are established for disease modeling and DILI prediction. Drawbacks for each of these seem inevitable, making the evaluation of their application domain and iDILI liability assessment potential crucial. A tiered approach could be considered, whereby compounds are initially screened and flagged using simple fit-for-purpose models for DILI prediction, followed by multicellular liver models that integrate the current knowledge of iDILI onset in combination with mechanistic readouts. Multiplexing models within an integrated mechanism-based testing strategy could improve the safety assessment accuracy. Defined in vitro models should integrate critical hepatocyte intrinsic risk factors as well as adaptive immune system components to refine iDILI liability assessment.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236282","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}

引用次数: 0

Interactions between phytotherapeutics and chemotherapeutics: the current evidence. 植物疗法和化学疗法之间的相互作用：目前的证据。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-10 DOI: 10.1080/17425255.2025.2517733

Sarah Allegra, Francesco Chiara, Giuliana Abbadessa, Asia Di Pietro, Maura Caudana, Silvia De Francia

{"title":"Interactions between phytotherapeutics and chemotherapeutics: the current evidence.","authors":"Sarah Allegra, Francesco Chiara, Giuliana Abbadessa, Asia Di Pietro, Maura Caudana, Silvia De Francia","doi":"10.1080/17425255.2025.2517733","DOIUrl":"https://doi.org/10.1080/17425255.2025.2517733","url":null,"abstract":"Introduction: The historical context of phytotherapy affects its potential as therapeutic products, and bioactive metabolites are crucial to the pharmacological effects, safety and effectiveness of alternative medicines.Areas covered: Phytotherapy is of great interest to cancer patients. Therefore, the purpose of this study was to gather publications about the interactions between chemotherapy and phytotherapeutics, medicinal plants, and similar formulations. To find publications published between January 2015 and January 2025, a MEDLINE PubMed search was conducted.Expert opinion: Several scientists and medical specialists have been looking into the potential of natural items to heal microbial cancer and chemotherapy-related adverse effects. The main factor influencing phytochemicals anticancer effectiveness is their ability to target a variety of pathways, including antimutagenic, antioxidant, and antiproliferative qualities. They can also regulate the host immune response to cancer by improving the surveillance of lymphocytes in cancer cells and lowering the inflammatory milieu. Because carcinogenesis is complex and involves a wide range of factors and signaling cascades, phytochemicals that target several targets may be useful anticancer drugs.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259680","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}

引用次数: 0

Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury. 药物代谢酶和转运体及其在药物性肝损伤发展中的作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-09 DOI: 10.1080/17425255.2025.2514537

AyoOluwa O Olubamiwa, Jingyi Ma, Patrice Dehanne, Catherine Noban, Yeliz Angın, Olivier Barberan, Minjun Chen

{"title":"Drug metabolizing enzymes and transporters, and their roles for the development of drug-induced liver injury.","authors":"AyoOluwa O Olubamiwa, Jingyi Ma, Patrice Dehanne, Catherine Noban, Yeliz Angın, Olivier Barberan, Minjun Chen","doi":"10.1080/17425255.2025.2514537","DOIUrl":"10.1080/17425255.2025.2514537","url":null,"abstract":"Introduction: Drug-induced liver injury (DILI) poses a significant challenge to drug development and human healthcare. The complex mechanisms underlying DILI make it challenging to accurately predict its occurrence, often leading to substantial financial losses from failed drug development projects and drug withdrawals. Growing evidence suggests that drug-metabolizing enzymes and transporters (DMETs) play a critical role in the development of DILI.Areas covered: In this review, we explore findings about the contributions of DMETs to DILI, with a focus on the studies examining genetic polymorphisms and their interactions with drugs. Additionally, we highlight the roles of DMETs in the development of predictive models for assessing DILI potential and in uncovering the mechanisms involved in DILI.Expert opinion: As new approach methods (NAMs) for assessing and predicting drug toxicity gain more prominence, it is imperative to better understand the adverse outcome pathways (AOPs) that underpin these methods. DMETs largely play a pivotal role in the molecular initiating events of DILI-related AOPs. Further research is needed to characterize DILI-related AOP networks and enhance the predictive performance of NAMs for assessing DILI risk.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251511","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}

引用次数: 0

Drug-drug interaction between anti-seizure medications in Dravet syndrome and Lennox-Gastaut syndrome. 抗癫痫药物在dravet综合征和lenox -胃综合征中的药物相互作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-07 DOI: 10.1080/17425255.2025.2510302

Roberta Roberti, Antonella Riva, Pasquale Striano, Emilio Russo

{"title":"Drug-drug interaction between anti-seizure medications in Dravet syndrome and Lennox-Gastaut syndrome.","authors":"Roberta Roberti, Antonella Riva, Pasquale Striano, Emilio Russo","doi":"10.1080/17425255.2025.2510302","DOIUrl":"10.1080/17425255.2025.2510302","url":null,"abstract":"Introduction: Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare, severe epileptic encephalopathies requiring complex, individualized treatment due to drug-resistant seizures, non-seizure outcomes, and comorbidities. Polytherapy is an inevitable aspect of managing these conditions, making the management of drug-drug interactions (DDIs) crucial for optimizing efficacy, minimizing toxicity, and addressing broader patient needs.Areas covered: This review discusses current and emerging pharmacological therapies for seizures in DS and LGS. We explore documented and theoretical DDIs between these drugs and other antiseizure medications (ASMs), focusing on pharmacokinetic and pharmacodynamic characteristics. The clinical significance of these DDIs is emphasized, with practical recommendations for their management.Expert opinion: Advances in understanding DDIs are key to optimizing treatment, particularly through the combination of ASMs with distinct mechanisms of action. A rational therapeutic approach should consider not only seizure control but also comorbidities. Understanding metabolic pathways involved in pharmacokinetic interactions is essential for predicting and avoiding adverse effects. Digital tools and decision-support apps can assist clinicians in quickly assessing DDIs and selecting the most effective drug combinations. Ongoing research in pharmacogenetics and personalized medicine holds promise for improving the management of complex conditions like DS and LGS, offering potential for better, individualized therapeutic strategies.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183406","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}

引用次数: 0

Practical perspectives on addressing hepatotoxicity during clinical candidate selection. 临床候选药物选择过程中处理肝毒性的实践观点。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-06 DOI: 10.1080/17425255.2025.2516048

Adrian S Ray

引用次数: 0

Pharmacotherapy in kidney disease: what it takes to move from general guidance to specific recommendations to stratified subgroups of patients - the tale of autosomal dominant polycystic kidney disease (ADPKD). 肾脏疾病的药物治疗：如何从一般指导转变为针对分层患者亚组的具体建议——常染色体显性多囊肾病（ADPKD）的故事

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-01 Epub Date: 2025-05-07 DOI: 10.1080/17425255.2025.2501127

Annika C Tillmann, Amin Rostami-Hodjegan, Jill Barber, Zubida M Al-Majdoub

{"title":"Pharmacotherapy in kidney disease: what it takes to move from general guidance to specific recommendations to stratified subgroups of patients - the tale of autosomal dominant polycystic kidney disease (ADPKD).","authors":"Annika C Tillmann, Amin Rostami-Hodjegan, Jill Barber, Zubida M Al-Majdoub","doi":"10.1080/17425255.2025.2501127","DOIUrl":"10.1080/17425255.2025.2501127","url":null,"abstract":"Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that leads to a range of systemic manifestations. Many of them require pharmacological interventions. Most patients receive multidrug therapy.Areas covered: The review summarizes prevalent ADPKD manifestations that might require pharmacological intervention and the most common drug therapies. It lists 2 to 3 prescribed drugs for each manifestation of ADPKD. The review identifies the drug transporters and drug-metabolizing enzymes associated with these drugs, as well as potential drug-drug interactions. To fulfill these aims, a literature search was conducted on PubMed, covering the period from 2021 to July 2024.Expert opinion: ADPKD therapy often focuses on treating a single manifestation of the disease. However, ADPKD is a complex condition that requires multidrug treatment. While doses of renally eliminated drugs are adjusted in ADPKD patients to account for renal function decline, the condition may change the expression and function of renal and hepatic drug-metabolizing enzymes and transporters, which could result in misevaluations in drug dosing in ADPKD patients and result in under- or overdosing, as well as drug-drug interactions. PBPK modeling offers a valuable tool to predict drug-drug interactions, preventing overdosing, and support precision dosing in patients with ADPKD.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"677-687"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059932","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}

引用次数: 0

DILI prediction in drug development: present and future. 药物开发中的DILI预测：现在和未来。

Expert opinion on drug metabolism & toxicology Pub Date : 2025-06-01 Epub Date: 2025-04-20 DOI: 10.1080/17425255.2025.2495955

Jack Uetrecht

{"title":"DILI prediction in drug development: present and future.","authors":"Jack Uetrecht","doi":"10.1080/17425255.2025.2495955","DOIUrl":"10.1080/17425255.2025.2495955","url":null,"abstract":"Introduction: Idiosyncratic drug-induced liver injury (iDILI) results in significant patient morbidity and significantly increases the risk of drug development. The current methods to screen for iDILI risk are inadequate.Areas covered: The general mechanism of iDILI and the current methods to screen for iDILI are reviewed. Then the potential for new biomarkers is explored.Expert opinion: Better biomarkers of iDILI risk should be based on the mechanism of iDILI. In general, it is an adaptive immune response, specifically CD8+ cytotoxic T cells, that is responsible for hepatocyte cell death, not direct toxicity of the drug. Therefore, in vitro cytotoxicity assays represent an artifact not the mechanism of iDILI. Activation of the adaptive immune response leading to iDILI requires an innate immune response, in particular activation of antigen presenting cells. The innate immune response is immediate and unlikely to be idiosyncratic. For example, studies have found that incubation of hepatocytes with drugs causes the release of molecules that activate THP-1-derived macrophages. The response of hepatocytes, the release of damage-associated molecular pattern molecules (DAMPs), especially in extracellular vesicles, and the response of antigen presenting cells (APCs) are likely to provide better biomarkers of iDILI risk.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"665-676"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035828","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}

引用次数: 0