Current drug metabolism最新文献

{"title":"Ceftobiprole and Cefiderocol for Patients on Extracorporeal Membrane Oxygenation: The Role of Therapeutic Drug Monitoring.","authors":"Diana Morales Castro, John Granton, Eddy Fan","doi":"10.2174/0113892002331260240919055056","DOIUrl":"10.2174/0113892002331260240919055056","url":null,"abstract":"<p><strong>Introduction: </strong>Limited data exist on therapeutic ranges for newer antimicrobials in the critically ill, with few pharmacokinetic studies including patients undergoing renal replacement therapy or extracorporeal membrane oxygenation (ECMO).</p><p><strong>Case representation: </strong>These interventions can potentially alter the pharmacokinetic profile of antibiotics, resulting in therapeutic failures, antimicrobial resistance, or increased toxicity. In this report, we present two ECMO patients treated with cefiderocol and ceftobiprole, where therapeutic drug monitoring (TDM) aided in the successful treatment of severe infections. Antibiotic trough concentrations in both cases were consistent with previously reported therapeutic levels in critically ill and ECMO patients, meeting minimal inhibitory concentrations recommended by the European Committee on Antimicrobial Susceptibility Testing for the respective pathogens.</p><p><strong>Conclusion: </strong>Treatment might be suboptimal if doses are not adjusted based on physicochemical properties and extracorporeal support. In an era marked by highly resistant pathogens, these cases highlight the importance of timely access to real-time TDM for optimizing and individualizing antimicrobial treatment.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"542-546"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Nanoscale Drug Delivery Strategies for Breast Carcinoma: A Comprehensive Exploration.","authors":"S Jaishree, Selvaraj Kousalya, S Prakash, D Vineesh","doi":"10.2174/0113892002298034240802110752","DOIUrl":"10.2174/0113892002298034240802110752","url":null,"abstract":"<p><p>Breast cancer (BC) is one of the major causes of poor health in women and the most devastating disease after lung cancer. The term \"cancer\" refers to a collection of problems resulting from abnormal cell proliferation, particularly cells that can spread to other parts of the body. Surgery, followed by chemotherapy or radiotherapy, is now accepted for BC-related cancers. However, chemotherapy and radiotherapy are rarely effective in the treatment of BC due to the adverse effects of these treatments on healthy tissues and organs. Consequently, the use of NPs in targeted Drug Delivery Systems (DDSs) has emerged as a promising strategy for BC treatment. This review provides a summary of recent clinical investigations of nanoparticle-mediated DDS that offer a novel therapeutic strategy commonly used for the treatment of breast cancer.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"391-402"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Metabolizing Enzymes: An Exclusive Guide into Latest Research in Pharmaco-genetic Dynamics in Arab Countries.","authors":"Laith Al Eitan, Iliya Yacoub Khair, Saif Alahmad","doi":"10.2174/0113892002323910240924145310","DOIUrl":"10.2174/0113892002323910240924145310","url":null,"abstract":"<p><p>Drug metabolizing enzymes play a crucial role in the pharmacokinetics and pharmacodynamics of therapeutic drugs, influencing their efficacy and safety. This review explores the impact of genetic polymorphisms in drug-metabolizing genes on drug response within Arab populations. We examine the genetic diversity specific to Arab countries, focusing on the variations in key drug-metabolizing enzymes such as CYP450, GST, and UGT families. The review highlights recent research on polymorphisms in these genes and their implications for drug metabolism, including variations in allele frequencies and their effects on therapeutic outcomes. Additionally, the paper discusses how these genetic variations contribute to the variability in drug response and adverse drug reactions among individuals in Arab populations. By synthesizing current findings, this review aims to provide a comprehensive understanding of the pharmacogenetic landscape in Arab countries and offer insights into personalized medicine approaches tailored to genetic profiles. The findings underscore the importance of incorporating pharmacogenetic data into clinical practice to enhance drug efficacy and minimize adverse effects, ultimately paving the way for more effective and individualized treatment strategies in the region.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"465-478"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Machine Learning Algorithms Evaluating the Single Nucleotide Polymorphisms of Metabolizing Enzymes with Clinical Outcomes Following Intravenous Paracetamol in Preterm Neonates with Patent Ductus Arteriosus.","authors":"Kannan Sridharan, George Priya Doss C, Hephzibah Cathryn R, Thirumal Kumar D, Muna Al Jufairi","doi":"10.2174/0113892002289238240222072027","DOIUrl":"10.2174/0113892002289238240222072027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Pharmacogenomics has been identified to play a crucial role in determining drug response. The present study aimed to identify significant genetic predictor variables influencing the therapeutic effect of paracetamol for new indications in preterm neonates.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Paracetamol has recently been preferred as a first-line drug for managing Patent Ductus Arteriosus (PDA) in preterm neonates. Single Nucleotide Polymorphisms (SNPs) in CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP3A4 have been observed to influence the therapeutic concentrations of paracetamol.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The purpose of this study was to evaluate various Machine Learning Algorithms (MLAs) and bioinformatics tools for identifying the key genotype predictor of therapeutic outcomes following paracetamol administration in neonates with PDA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Preterm neonates with hemodynamically significant PDA were recruited in this prospective, observational study. The following SNPs were evaluated: CYP2E1*5B, CYP2E1*2, CYP3A4*1B, CYP3A4*2, CYP3A4*3, CYP3A5*3, CYP3A5*7, CYP3A5*11, CYP1A2*1C, CYP1A2*1K, CYP1A2*3, CYP1A2*4, CYP1A2*6, and CYP2D6*10. Amongst the MLAs, Artificial Neural Network (ANN), C5.0 algorithm, Classification and Regression Tree analysis (CART), discriminant analysis, and logistic regression were evaluated for successful closure of PDA. Generalized linear regression, ANN, CART, and linear regression were used to evaluate maximum serum acetaminophen concentrations. A two-step cluster analysis was carried out for both outcomes. Area Under the Curve (AUC) and Relative Error (RE) were used as the accuracy estimates. Stability analysis was carried out using &lt;i&gt;in silico&lt;/i&gt; tools, and Molecular Docking and Dynamics Studies were carried out for the above-mentioned enzymes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Two-step cluster analyses have revealed CYP2D6*10 and CYP1A2*1C to be the key predictors of the successful closure of PDA and the maximum serum paracetamol concentrations in neonates. The ANN was observed with the maximum accuracy (AUC = 0.53) for predicting the successful closure of PDA with CYP2D6*10 as the most important predictor. Similarly, ANN was observed with the least RE (1.08) in predicting maximum serum paracetamol concentrations, with CYP2D6*10 as the most important predictor. Further MDS confirmed the conformational changes for P34A and P34S compared to the wildtype structure of CYP2D6 protein for stability, flexibility, compactness, hydrogen bond analysis, and the binding affinity when interacting with paracetamol, respectively. The alterations in enzyme activity of the mutant CYP2D6 were computed from the molecular simulation results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;We have identified CYP2D6*10 and CYP1A2*1C polymorphisms to significantly predict the therapeutic outcomes following the administration of paracetamol in preterm neonates with PDA. Prospective studies are required","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"128-139"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UPLC-LTQ-Orbitrap Study on Rat Urinary Metabolites of 5-Methoxy-Alpha-Methyltryptamine.","authors":"Guo Zhutao, Keran Ding, Shuiqing Zheng, Chunfang Ni, Chen Liang, Siyang He, Qianya Deng","doi":"10.2174/0113892002295551240628061732","DOIUrl":"10.2174/0113892002295551240628061732","url":null,"abstract":"<p><strong>Objective: </strong>5-Methoxy-α-Methyltryptamine (5-MeO-AMT) is a new psychoactive substance which is abused due to its hallucinogenic and euphoric effects. This study aimed to study the metabolic characteristics of 5-MeO-AMT.</p><p><strong>Methods: </strong>Five rats were given intraperitoneal injection at a dose of 50 mg/kg of 5-MeO-AMT, and their urine was subsequently collected at different times within 7 days. Ultra-high performance liquid chromatographytandem high-resolution mass spectrometry (UPLC-LTQ-Orbitrap) was used to detect the precise molecular weight and fragment ions of 5-MeO-AMT and its possible metabolites in the urine sample extracted with benzene-ethyl acetate.</p><p><strong>Results: </strong>Three metabolites, including OH-5-MeO-AMT, α-Me-5-HT, and N-Acetyl-5-MeO-AMT were identified in rats' urine. The major metabolic pathways involved O-demethylation, hydroxylation of indole ring, and Acetylation on aliphatic amines.</p><p><strong>Conclusion: </strong>The results of this study are an important reference for the identification and screening of toxicants of 5-MeO-AMT.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"298-305"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Hot Melt Extruded Co-Formulated Artesunate and Amodiaquine- Soluplus^® Solid Dispersion System in Fixed-Dose Form: Amorphous State Characterization and Pharmacokinetic Evaluation.","authors":"Md Ali Mujtaba, Ritesh Fule, Purnima Amin, Gamal Osman Elhassan, Meshal Meteab Majed Almoutairi, Mohammed Kaleem, Musarrat Husain Warsi","doi":"10.2174/0113892002330772240912055518","DOIUrl":"10.2174/0113892002330772240912055518","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to develop co-amorphous Solid Dispersion (SD) system containing antimalarials Artesunate (ARS) and Amodiaquine (AMQ) to improve its oral bioavailability employing the Hot Melt Extrusion (HME) technique. Soluplus^® was selected as a polymeric excipient, whereas Lutrol F127, Lutrol F68, TPGS, and PEG400 as surfactants were incorporated along with Soluplus^® to enhance extrudability, improve hydrophilicity, and improve the blend viscosity during HME. Soluplus^® with surfactant combination successfully stabilizes both drugs during extrusion by generating SD because of its lower glass transition temperature (Tg) and viscoelastic behavior.</p><p><strong>Methods: </strong>Physicochemical characterizations were performed using FTIR, DSC, TGA, and XRD, which confirmed the amorphousization of drugs in the SD system. The molecular level morphology of the optimized formulation was quantified using high-resolution techniques such as Atomic-Force Microscopy (AFM), Raman spectral, and mapping analysis. The transition of the crystalline drugs into a stable amorphous form has been demonstrated by 1H-NMR and 2D-NMR studies. The <i>in vivo</i> pharmacokinetics study in rats showed that the SD-containing drug-Soluplus-TPGS (FDC10) formulation has 36.63-56.13 (ARS-AMQ) folds increase in the Cmax and 41.87-54.34 (ARS-AMQ) folds increase AUC (0-72) as compared to pure drugs.</p><p><strong>Results: </strong>Pharmacokinetic analysis shows that a fixed-dose combination of 50:135 mg of both APIs (ARSAMQ) significantly increased oral bioavailability by elevating Cmax and AUC, in comparison to pure APIs and also better than the marketed product Coarsucam^®.</p><p><strong>Conclusion: </strong>Therefore, the developed melt extruded co-amorphous formulation has enhanced bioavailability and has more effectiveness than the marketed product Coarsucam^®. .</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"505-522"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lingguizhugan Decoction Improved Obesity by Modulating the Gut Microbiota and its Metabolites in Mice.","authors":"Meiling Wang, Hairong Li, Chunmei Liu, Yuanyuan Zhang, Qian Wu, Yubin Yang","doi":"10.2174/0113892002289388240705113755","DOIUrl":"10.2174/0113892002289388240705113755","url":null,"abstract":"<p><strong>Background: </strong>The global obese population is rapidly increasing, urgently requiring the development of effective and safe weight-loss medications. The classic Chinese medicine formulation Lingguizhugan Decoction has exerted a significant anti-obesity effect. However, the underlying mechanism is still unclear.</p><p><strong>Objective: </strong>This study aimed to explore the mechanism of LGZGD in the treatment of obesity based on the gut microbiota and its metabolites.</p><p><strong>Methods: </strong>Three different dosages of LGZGD were gavaged to ob/ob mice for 8 weeks. Body mass and visceral fat mass were evaluated. Additionally, the changes in gut microbiota, fecal and plasma metabolites in mice after LGZGD treatment were analyzed by metagenomics and non-targeted metabolomics.</p><p><strong>Results: </strong>The results demonstrated a significant anti-obesity effect of LGZGD treatment in ob/ob mice. Furthermore, the metagenomic analysis revealed that LGZGD reduced the ratio of <i>Firmicutes / Bacteroidetes</i> (<i>F</i> to <i>B</i>) in the gut, restored gut microbiota diversity, and identified 3 enriched KEGG pathways, including energy metabolism, lipid metabolism, and energy production and conversion pathways. Based on non-targeted metabolomics analysis, 20 key metabolites in the feces and 30 key metabolites in the plasma responding to LGZGD treatment were identified, and the levels of Eicosapentaenoic acid (EPA) and Myristoleic acid (MA) might be the metabolites related to gut microbiota after LGZGD treatment. Their biological functions were mainly related to the metabolism pathway.</p><p><strong>Conclusions: </strong>These findings suggested that LGZGD had therapeutic potential for obesity. The mechanism of LGZGD alleviating obesity was associated with improving dysbiosis of the gut microbiota. LDZGD affected gut microbiota-derived metabolites of EPA and MA and may act on energy metabolism pathways.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"276-287"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy.","authors":"Michael Murray","doi":"10.2174/0113892002288832240213095622","DOIUrl":"10.2174/0113892002288832240213095622","url":null,"abstract":"<p><p>Asunaprevir, daclatasvir, and beclabuvir are direct-acting antiviral agents used in the treatment of patients infected with hepatitis C genotype 1b. This article reviews the biotransformation and disposition of these drugs in relation to the safety and efficacy of therapy. CYP3A4 and 3A5 catalyze the oxidative biotransformation of the drugs, while P-glycoprotein mediates their efflux from tissues. Asunaprevir is also a substrate for the influx transporters OATP1B1 and OATP2B1 and the efflux transporter MRP2, while beclabuvir is also a substrate for the efflux transporter BCRP. Liver disease decreases the expression of CYPs and transporters that mediate drug metabolism and disposition. Serum asunaprevir concentrations, but not those of daclatasvir or beclabuvir, are increased in patients with severe liver disease, which may produce toxicity. Pharmacogenomic variation in CYPs and transporters also has the potential to disrupt therapy with asunaprevir, daclatasvir and beclabuvir; some variants are more prevalent in certain racial groups. Pharmacokinetic drug-drug interactions, especially where asunaprevir, daclatasvir, and beclabuvir are victim drugs, are mediated by coadministered rifampicin, ketoconazole and ritonavir, and are attributable to inhibition and/or induction of CYPs and transporters. Conversely, there is also evidence that asunaprevir, daclatasvir and beclabuvir are perpetrators of drug interactions with coadministered rosuvastatin and dextromethorphan. Together, liver disease, pharmacogenomic variation and drug-drug interactions may disrupt therapy with asunaprevir, daclatasvir and beclabuvir due to the impaired function of important CYPs and transporters.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"96-109"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Trends in Hybrid Nanoparticles: Revolutionary Advances and Promising Biomedical Applications.","authors":"Harish Bhardwaj, Sulekha Khute, Ram Kumar Sahu, Rajendra Kumar Jangde","doi":"10.2174/0113892002291778240610073122","DOIUrl":"10.2174/0113892002291778240610073122","url":null,"abstract":"<p><p>Modern nanostructures must fulfill a wide range of functions to be valuable, leading to the combination of various nano-objects into hierarchical assemblies. Hybrid Nanoparticles (HNPs), comprised of multiple types of nanoparticles, are emerging as nanoscale structures with versatile applications. HNPs offer enhanced medical benefits compared to basic combinations of distinct components. They address the limitations of traditional nanoparticle delivery systems, such as poor water solubility, nonspecific targeting, and suboptimal therapeutic outcomes. HNPs also facilitate the transition from anatomical to molecular imaging in lung cancer diagnosis, ensuring precision. In clinical settings, the selection of nanoplatforms with superior reproducibility, cost-effectiveness, easy preparation, and advanced functional and structural characteristics is paramount. This study aims toextensively examine hybrid nanoparticles, focusing on their classification, drug delivery mechanisms, properties of hybrid inorganic nanoparticles, advancements in hybrid nanoparticle technology, and their biomedical applications, particularly emphasizing the utilization of smart hybrid nanoparticles. PHNPs enable the delivery of numerous anticancer, anti-leishmanial, and antifungal drugs, enhancing cellular absorption, bioavailability, and targeted drug delivery while reducing toxic side effects.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"248-265"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-Drug Interaction Potential of Remimazolam: CYP 450, Transporters, and Protein Binding.","authors":"Karl-Uwe Petersen, Wolfgang Schmalix, Marija Pesic, Thomas Stöhr","doi":"10.2174/0113892002300657240521094732","DOIUrl":"10.2174/0113892002300657240521094732","url":null,"abstract":"<p><strong>Background: </strong>The ultra-short-acting benzodiazepine, remimazolam, is a new treatment modality for procedural sedation and general anesthesia. Its activity is terminated by carboxylesterase 1 (CES1).</p><p><strong>Objective: </strong>The objective of this study was to determine the drug-drug interaction (DDI) potential of remimazolam through mechanisms unrelated to its metabolizing enzyme, CES1.</p><p><strong>Methods: </strong>Conventional in vitro co-exposure experiments were conducted to study possible interactions of remimazolam and its primary metabolite, CNS7054, mediated by competitive binding to plasma protein or reactions with cytochrome P450 isoforms or drug transporters.</p><p><strong>Results: </strong>No relevant interactions of remimazolam or its metabolite with cytochrome P450 (CYP) isoforms at clinically relevant concentrations were identified. Likewise, standard experiments revealed no clinically relevant interactions with drug transporters and plasma proteins.</p><p><strong>Conclusion: </strong>The present data and analyses suggest a very low potential of remimazolam for pharmacokinetic DDIs mediated by CYP isoforms, drug transporters, and protein binding.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"266-275"},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}