Expert opinion on drug metabolism & toxicology最新文献_第8页

New-generation androgen receptor signaling inhibitors (ARSIs) in metastatic hormone-sensitive prostate cancer (mHSPC): pharmacokinetics, drug-drug interactions (DDIs), and clinical impact. 新一代雄激素受体信号抑制剂（ARSIs）在转移性激素敏感性前列腺癌（mHSPC）中的应用：药代动力学、药物间相互作用（DDIs）和临床影响。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-06-01 Epub Date: 2024-05-22 DOI: 10.1080/17425255.2024.2353749

Lorenzo Gasperoni, Emilio Francesco Giunta, Daniela Montanari, Carla Masini, Ugo De Giorgi

{"title":"New-generation androgen receptor signaling inhibitors (ARSIs) in metastatic hormone-sensitive prostate cancer (mHSPC): pharmacokinetics, drug-drug interactions (DDIs), and clinical impact.","authors":"Lorenzo Gasperoni, Emilio Francesco Giunta, Daniela Montanari, Carla Masini, Ugo De Giorgi","doi":"10.1080/17425255.2024.2353749","DOIUrl":"10.1080/17425255.2024.2353749","url":null,"abstract":"Introduction: The therapeutic scenario of metastatic hormone-sensitive prostate cancer (mHSPC) has dramatically changed in recent years, with the approval of new-generation Androgen Receptor Signaling Inhibitors (ARSIs), in combination with the androgen deprivation therapy (ADT), which was the previous standard of care. Despite showing a similar clinical efficacy, ARSIs, all of which are administered orally, are different in terms of pharmacokinetic and drug-drug interactions (DDIs).Areas covered: This review covers the main pharmacokinetic characteristics of ARSIs that have been approved for the first-line therapy of mHSPC patients, underlying the differences among these molecules and focusing on the known or possible interactions with other drugs. Full-text articles and abstracts were searched in PubMed.Expert opinion: Since prostate cancer occurs mainly in older age, comorbidities and the consequent polypharmacy increase the DDI risk in mHSPC patients who are candidates for ARSI. Waiting for new therapeutic options, in the absence of direct comparisons, pharmacokinetic knowledge is essential to guide clinicians in prescribing ARSI in this setting.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"491-502"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080807","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

Recent advances in cell-based in vitro models for predicting drug permeability across brain, intestinal, and pulmonary barriers. 基于细胞的体外模型在预测药物跨脑、肠和肺屏障渗透性方面的最新进展。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-06-01 Epub Date: 2024-06-13 DOI: 10.1080/17425255.2024.2366390

Bassma Eltanameli, Janny Piñeiro-Llanes, Rodrigo Cristofoletti

{"title":"Recent advances in cell-based in vitro models for predicting drug permeability across brain, intestinal, and pulmonary barriers.","authors":"Bassma Eltanameli, Janny Piñeiro-Llanes, Rodrigo Cristofoletti","doi":"10.1080/17425255.2024.2366390","DOIUrl":"10.1080/17425255.2024.2366390","url":null,"abstract":"Introduction: Recent years have witnessed remarkable progress in the development of cell-based in vitro models aimed at predicting drug permeability, particularly focusing on replicating the barrier properties of the blood-brain barrier (BBB), intestinal epithelium, and lung epithelium.Area covered: This review provides an overview of 2D in vitro platforms, including monocultures and co-culture systems, highlighting their respective advantages and limitations. Additionally, it discusses tools and techniques utilized to overcome these limitations, paving the way for more accurate predictions of drug permeability. Furthermore, this review delves into emerging technologies, particularly microphysiological systems (MPS), encompassing static platforms such as organoids and dynamic platforms like microfluidic devices. Literature searches were performed using PubMed and Google Scholar. We focus on key terms such as in vitro permeability models, MPS, organoids, intestine, BBB, and lungs.Expert opinion: The potential of these MPS to mimic physiological conditions more closely offers promising avenues for drug permeability assessment. However, transitioning these advanced models from bench to industry requires rigorous validation against regulatory standards. Thus, there is a pressing need to validate MPS to industry and regulatory agency standards to exploit their potential in drug permeability prediction fully. This review underscores the importance of such validation processes to facilitate the translation of these innovative technologies into routine pharmaceutical practice.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"439-458"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141289079","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

Understanding the impact of ABCG2 polymorphisms on drug pharmacokinetics: focus on rosuvastatin and allopurinol. 了解 ABCG2 多态性对药物药代动力学的影响：聚焦罗伐他汀和别嘌醇。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-06-01 Epub Date: 2024-06-04 DOI: 10.1080/17425255.2024.2362184

Anne Kasten, Ingolf Cascorbi

{"title":"Understanding the impact of ABCG2 polymorphisms on drug pharmacokinetics: focus on rosuvastatin and allopurinol.","authors":"Anne Kasten, Ingolf Cascorbi","doi":"10.1080/17425255.2024.2362184","DOIUrl":"10.1080/17425255.2024.2362184","url":null,"abstract":"Introduction: In addition to the well-established understanding of the pharmacogenetics of drug-metabolizing enzymes, there is growing data on the effects of genetic variation in drug transporters, particularly ATP-binding cassette (ABC) transporters. However, the evidence that these genetic variants can be used to predict drug effects and to adjust individual dosing to avoid adverse events is still limited.Areas covered: This review presents a summary of the current literature from the PubMed database as of February 2024 regarding the impact of genetic variants on ABCG2 function and their relevance to the clinical use of the HMG-CoA reductase inhibitor rosuvastatin and the xanthine oxidase inhibitor allopurinol.Expert opinion: Although there are pharmacogenetic guidelines for the ABCG2 missense variant Q141K, there is still some conflicting data regarding the clinical benefits of these recommendations. Some caution appears to be warranted in homozygous ABCG2 Q141K carriers when rosuvastatin is administered at higher doses and such information is already included in the drug label. The benefit of dose adaption to lower possible side effects needs to be evaluated in prospective clinical studies.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"519-528"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163115","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

Genetic polymorphisms of drug-metabolizing enzymes in older and newer anti-seizure medications. 新旧抗癫痫药物中药物代谢酶的基因多态性。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-06-01 Epub Date: 2024-05-31 DOI: 10.1080/17425255.2024.2362190

Gianluca D'Onofrio, Andrea Santangelo, Antonella Riva, Pasquale Striano

引用次数: 0

Induction effect of antiretroviral bictegravir on the expression of Abcb1, Abcg2 and Abcc1 genes associated with P-gp, BCRP and MRP1 transporters present in rat peripheral blood mononuclear cells. 抗逆转录病毒药物比特拉韦对大鼠外周血单核细胞中与 P-gp、Bcrp 和 Mrp1 转运体相关的 Abcb1、Abcg2 和 Abcc1 基因表达的诱导作用。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-06-01 Epub Date: 2024-05-13 DOI: 10.1080/17425255.2024.2352462

Tarang Jadav, Niraj Rajput, Hemant Kumar, Santosh Kumar Behera, Pinaki Sengupta

{"title":"Induction effect of antiretroviral bictegravir on the expression of Abcb1, Abcg2 and Abcc1 genes associated with P-gp, BCRP and MRP1 transporters present in rat peripheral blood mononuclear cells.","authors":"Tarang Jadav, Niraj Rajput, Hemant Kumar, Santosh Kumar Behera, Pinaki Sengupta","doi":"10.1080/17425255.2024.2352462","DOIUrl":"10.1080/17425255.2024.2352462","url":null,"abstract":"Background: Antiretrovirals have the potential to cause drug interactions leading to inefficacy or toxicity via induction of efflux transporters through nuclear receptors, altering drug concentrations at their target sites.Research design and methods: This study used molecular dynamic simulations and qRT-PCR to investigate bictegravir's interactions with nuclear receptors PXR and CAR, and its effects on efflux transporters (P-gp, BCRP, MRP1) in rat PBMCs. PBMC/plasma drug concentrations were measured using LC-MS/MS to assess the functional impact of transporter expression.Results: Bictegravir significantly increased the expression of ABC transporters, with Car identified as a key mediator. This suggests that bictegravir's influence on nuclear receptors could affect drug transport and efficacy at the cellular level.Conclusions: Bictegravir activates nuclear receptors enhancing efflux transporter expression. Understanding these interactions is crucial for preventing drug-drug interactions and reducing toxicity in clinical use. Combining CAR antagonists with bictegravir may prevent drug resistance and toxicity. However, these findings are based on preclinical data and necessitate further clinical trials to confirm their applicability in clinical settings.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"529-539"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864190","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

An update on microfluidic multi-organ-on-a-chip systems for reproducing drug pharmacokinetics: the current state-of-the-art. 用于再现药物药代动力学的微流控芯片多器官系统的最新进展：当前最新技术。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-06-01 Epub Date: 2024-06-04 DOI: 10.1080/17425255.2024.2362183

Mateo Gabriel Vasconez Martinez, Martin Frauenlob, Mario Rothbauer

{"title":"An update on microfluidic multi-organ-on-a-chip systems for reproducing drug pharmacokinetics: the current state-of-the-art.","authors":"Mateo Gabriel Vasconez Martinez, Martin Frauenlob, Mario Rothbauer","doi":"10.1080/17425255.2024.2362183","DOIUrl":"10.1080/17425255.2024.2362183","url":null,"abstract":"Introduction: Advances in the accessibility of manufacturing technologies and iPSC-based modeling have accelerated the overall progress of organs-on-a-chip. Notably, the progress in multi-organ systems is not progressing with equal speed, indicating that there are still major technological barriers to overcome that may include biological relevance, technological usability as well as overall accessibility.Areas covered: We here review the progress in the field of multi-tissue- and body-on-a-chip pre and post- SARS-CoV-2 pandemic and review five selected studies with increasingly complex multi-organ chips aiming at pharmacological studies.Expert opinion: We discuss future and necessary advances in the field of multi-organ chips including how to overcome challenges regarding cell diversity, improved culture conditions, model translatability as well as sensor integrations to enable microsystems to cover organ-organ interactions in not only toxicokinetic but more importantly pharmacodynamic and -kinetic studies.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"459-471"},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238729","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

Pharmacokinetic evaluation of donanemab for the treatment of Alzheimer's. 多奈单抗治疗阿尔茨海默氏症的药代动力学评估。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-05-20 DOI: 10.1080/17425255.2024.2357637

Tanya Song, Yunfei Wang, Bret David Silverglate, George T Grossberg

{"title":"Pharmacokinetic evaluation of donanemab for the treatment of Alzheimer's.","authors":"Tanya Song, Yunfei Wang, Bret David Silverglate, George T Grossberg","doi":"10.1080/17425255.2024.2357637","DOIUrl":"10.1080/17425255.2024.2357637","url":null,"abstract":"Introduction: Donanemab is a humanized monoclonal antibody that significantly reduces cerebral amyloid plaques in Alzheimer's Disease (AD). It can delay disease progression and cognitive decline, making it one of the most promising disease-modifying treatments in the current treatment landscape.Areas covered: This paper covers the current literature available on pharmacokinetics, pharmacodynamics, safety, and tolerability of donanemab. Publications from PubMed and Google were reviewed. A summary of regulatory approvals and current clinical data is also provided.Expert opinion/commentary: Donanemab as a therapy for AD has more effective disease-modifying effects compared to lecanemab. Donanemab appears generally well-tolerated; however, it may have higher rates of severe side effects, such as amyloid-related imaging abnormalities (ARIA), that could lead to death. Guidelines for frequency of MRI monitoring for ARIA/safety are pending but will be integral to determining its use. Despite some limitations, donanemab is expected to receive FDA approval, giving clinicians access to another disease-modifying drug. Overall, more data is needed about donanemab, especially relating to safety, efficacy, cost, and integration with other treatments, but its development signifies progress in AD treatment.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961251","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 role of the circadian timing system on drug metabolism and detoxification: an update. 昼夜节律计时系统对药物代谢和解毒的作用：最新进展。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-05-20 DOI: 10.1080/17425255.2024.2356167

Alper Okyar, Dilek Ozturk Civelek, Yasemin Kubra Akyel, Saliha Surme, Zeliha Pala Kara, I Halil Kavakli

{"title":"The role of the circadian timing system on drug metabolism and detoxification: an update.","authors":"Alper Okyar, Dilek Ozturk Civelek, Yasemin Kubra Akyel, Saliha Surme, Zeliha Pala Kara, I Halil Kavakli","doi":"10.1080/17425255.2024.2356167","DOIUrl":"10.1080/17425255.2024.2356167","url":null,"abstract":"Introduction: The 24-hour variations in drug absorption, distribution, metabolism, and elimination, collectively known as pharmacokinetics, are fundamentally influenced by rhythmic physiological processes regulated by the molecular clock. Recent advances have elucidated the intricacies of the circadian timing system and the molecular interplay between biological clocks, enzymes and transporters in preclinical level.Area covered: Circadian rhythm of the drug metabolizing enzymes and carrier efflux functions possess a major role for drug metabolism and detoxification. The efflux and metabolism function of intestines and liver seems important. The investigations revealed that the ABC and SLC transporter families, along with cytochrome p-450 systems in the intestine, liver, and kidney, play a dominant role in the circadian detoxification of drugs. Additionally, the circadian control of efflux by the blood-brain barrier is also discussed.Expert opinion: The influence of the circadian timing system on drug pharmacokinetics significantly impacts the efficacy, adverse effects, and toxicity profiles of various drugs. Moreover, the emergence of sex-related circadian changes in the metabolism and detoxification processes has underscored the importance of considering gender-specific differences in drug tolerability and pharmacology. A better understanding of coupling between central clock and circadian metabolism/transport contributes to the development of more rational drug utilization and the implementation of chronotherapy applications.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961254","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

Cephalosporins with warfarin increase the risk of bleeding: myth or fact? 头孢菌素与华法林合用会增加出血风险：传说还是事实？

Expert opinion on drug metabolism & toxicology Pub Date : 2024-05-01 Epub Date: 2024-05-09 DOI: 10.1080/17425255.2024.2349718

Abrar K Thabit, Samaher Y Almoalim, Rahaf Altalhi

引用次数: 0

Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review. 羧基酯酶的调节及其对药物动力学和药效学的影响：最新综述。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-05-01 Epub Date: 2024-05-06 DOI: 10.1080/17425255.2024.2348491

Yaping Liu, Jiapeng Li, Hao-Jie Zhu

{"title":"Regulation of carboxylesterases and its impact on pharmacokinetics and pharmacodynamics: an up-to-date review.","authors":"Yaping Liu, Jiapeng Li, Hao-Jie Zhu","doi":"10.1080/17425255.2024.2348491","DOIUrl":"10.1080/17425255.2024.2348491","url":null,"abstract":"Introduction: Carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2) are among the most abundant hydrolases in humans, catalyzing the metabolism of numerous clinically important medications, such as methylphenidate and clopidogrel. The large interindividual variability in the expression and activity of CES1 and CES2 affects the pharmacokinetics (PK) and pharmacodynamics (PD) of substrate drugs.Areas covered: This review provides an up-to-date overview of CES expression and activity regulations and examines their impact on the PK and PD of CES substrate drugs. The literature search was conducted on PubMed from inception to January 2024.Expert opinion: Current research revealed modest associations of CES genetic polymorphisms with drug exposure and response. Beyond genomic polymorphisms, transcriptional and posttranslational regulations can also significantly affect CES expression and activity and consequently alter PK and PD. Recent advances in plasma biomarkers of drug-metabolizing enzymes encourage the research of plasma protein and metabolite biomarkers for CES1 and CES2, which could lead to the establishment of precision pharmacotherapy regimens for drugs metabolized by CESs. Moreover, our understanding of tissue-specific expression and substrate selectivity of CES1 and CES2 has shed light on improving the design of CES1- and CES2-activated prodrugs.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"377-397"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0