Expert opinion on drug metabolism & toxicology最新文献_第4页

Methadone metabolism and cytochrome P450 polymorphisms: a systematic review and meta-analysis. 美沙酮代谢与细胞色素 P450 多态性：系统回顾与荟萃分析。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-11-28 DOI: 10.1080/17425255.2024.2432664

Seenae Eum, Nicholas P Vernacchia, Nia Doughty, Sahar Mehrzad, Andrew H Talal, Fatemeh Chalabianloo, Evan D Kharasch

{"title":"Methadone metabolism and cytochrome P450 polymorphisms: a systematic review and meta-analysis.","authors":"Seenae Eum, Nicholas P Vernacchia, Nia Doughty, Sahar Mehrzad, Andrew H Talal, Fatemeh Chalabianloo, Evan D Kharasch","doi":"10.1080/17425255.2024.2432664","DOIUrl":"https://doi.org/10.1080/17425255.2024.2432664","url":null,"abstract":"Introduction: Confusion regarding methadone metabolism exists, hampering optimal clinical use. A systematic review was conducted to assess the impacts of cytochrome P450 (CYP) genetic polymorphisms on methadone outcomes.Methods: MEDLINE, EMBASE, Web of Science, PsycINFO, and CENTRAL were searched to identify studies reporting methadone dose-adjusted plasma concentrations, clearance, maintenance dose, or treatment response in relation to CYP polymorphisms in humans. ROBINS-I was used to evaluate risk of bias in included studies. Each outcome was synthesized for each CYP using the ratio of means or odds ratio as the effect size measure.Results: Ten, two, fourteen, and five studies were included in the meta-analyses of the concentration, clearance, dose, and treatment response, respectively. The CYP2B6 c.516 G>T variant was robustly associated with (S)-methadone concentrations (GT+TTvs.GG: ratio of means (RoM) 1.40, p < 0.01) and clearance (GT+TTvs.GG: RoM 0.65, p < 0.01) but less with (R)- or (R,S)-methadone. The CYP2B6 variant also affected methadone dose for opioid use disorder (GT+TTvs.GG: RoM 0.93, p = 0.04). CYP2C19, CYP2C9, CYP2D6, and CYP3A5 polymorphisms did not influence any of the assessed outcomes.Conclusions: CYP2B6 genetics had statistically significant impacts on (S)-methadone and less so on (R)-methadone exposure and clearance and was statistically significantly but not clinically meaningfully associated with dose requirements.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741795","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

A novel in vivo approach to monitoring Cyp3a induction and inhibition by bioluminescent urinalysis. 生物发光尿液分析监测Cyp3a诱导和抑制的一种新的体内方法。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-11-28 DOI: 10.1080/17425255.2024.2434645

James J Cali, Dongping Ma, Katarina Bohm, Dieter H Klaubert

{"title":"A novel in vivo approach to monitoring Cyp3a induction and inhibition by bioluminescent urinalysis.","authors":"James J Cali, Dongping Ma, Katarina Bohm, Dieter H Klaubert","doi":"10.1080/17425255.2024.2434645","DOIUrl":"https://doi.org/10.1080/17425255.2024.2434645","url":null,"abstract":"Background: Adverse drug-drug interactions (DDI) may occur when one drug accelerates or slows a second drug's metabolism by, respectively, inducing or inhibiting a cytochrome P450 (CYP) that metabolizes that second drug. We developed an in vivo method employing urinalysis to complement in vitro CYP induction and inhibition measurements widely used to predict DDIs.Research design and methods: Focusing on Cyp3a enzymes, the major mammalian drug metabolizers, we applied luciferin-IPA, a selective Cyp3a probe substrate to mice after Cyp3a inducers and inhibitor treatments. Cyp3a converts the probe to a metabolite that is eliminated in urine and drives light output when mixed with a luciferase reaction mixture. We hypothesized that urine from an initial renal elimination phase would, respectively, drive elevated or reduced light output as a reflection of Cyp3a induction or inhibition.Results: Luciferase mixed with urine from Cyp3a-induced mice showed enhanced signals, while a Cyp3a inhibitor diminished induced and basal signals versus vehicle.Conclusions: A Cyp3a-selective luminogenic probe substrate enables rapid urinalysis-based testing for detecting Cyp3a induction and inhibition and predicting Cyp3a-dependent DDIs. The study serves as a proof of concept for using caged luciferins for in vivo enzyme activity tests with a readily accessible sample type.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752530","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

A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects. 一项三臂临床研究，比较健康男性受试者体内地诺单抗生物仿制药 LY06006 与参考药物地诺单抗的药代动力学和药效学相似性。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-11-24 DOI: 10.1080/17425255.2024.2432673

Rainard Fuhr, Xuejiao Sun, Xi Wang, Ying Dong, Joe Tai, Ming Zhou, Changlin Dou

{"title":"A three-arm clinical study to compare pharmacokinetic and pharmacodynamic similarity of the denosumab biosimilar LY06006 with reference denosumab in healthy male subjects.","authors":"Rainard Fuhr, Xuejiao Sun, Xi Wang, Ying Dong, Joe Tai, Ming Zhou, Changlin Dou","doi":"10.1080/17425255.2024.2432673","DOIUrl":"10.1080/17425255.2024.2432673","url":null,"abstract":"Background: This study aimed to evaluate the pharmacokinetic (PK), pharmacodynamic (PD) similarity, comparable safety, and immunogenicity between LY06006, European Union-sourced denosumab (EU-DEN), and United States-sourced denosumab (US-DEN).Research design and methods: In this double-blind, parallel-group, and single-dose study, 300 healthy male subjects were randomized 1:1:1 to receive a 60 mg dose of either LY06006, EU-DEN, or US-DEN subcutaneously. This study lasted for 253 days. Primary PK endpoints included maximum serum concentration (Cmax), area under the concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC0-t), and AUC from time zero to infinity (AUC0-inf). Pharmacokinetic equivalence was concluded if the two-sided 90% confidence interval (CI) for the geometric least squares mean ratio (GLSMR) of primary endpoints were within 80%-125%. Other PK parameters, PD parameters, safety, and immunogenicity assessments were also conducted during the study.Results: The 90% CIs for ratios of GLSMR were within the predefined equivalence margin for AUC0-inf (89.0%-111.1%), AUC0-t (89.7%-111.3%), and Cmax (92.3%-106.7%). The PD parameters, safety, and immunogenicity of LY06006 were also comparable to US-DEN and EU-DEN.Conclusion: LY06006 was highly similar to US-DEN and EU-DEN in terms of PK, PD, safety and immunogenicity in healthy male subjects.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06095427.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712290","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 bictegravir + emtricitabine + tenofovir alafenamide in HIV treatment. 比特拉韦+恩曲他滨+替诺福韦-阿拉非那胺在艾滋病治疗中的药代动力学评估。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-11-13 DOI: 10.1080/17425255.2024.2428820

Elena Bruzzesi, Camilla Muccini, Antonella Castagna

{"title":"Pharmacokinetic evaluation of bictegravir + emtricitabine + tenofovir alafenamide in HIV treatment.","authors":"Elena Bruzzesi, Camilla Muccini, Antonella Castagna","doi":"10.1080/17425255.2024.2428820","DOIUrl":"https://doi.org/10.1080/17425255.2024.2428820","url":null,"abstract":"Introduction: The combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) represents a valid option of antiretroviral therapy (ART) as first line regimen both in ART-naïve and -experienced people with HIV (PWH). This review evaluates the pharmacokinetic profiles of these drugs and their clinical implications.Areas covered: This article discusses the pharmacokinetics and pharmacodynamics of BIC/FTC/TAF. It covers their efficacy, safety, tolerability, and potential drug-drug interactions. It also examines the benefits of this combination therapy, including improved adherence due to once-daily dosing and reduced toxicity compared to previous therapies. The review includes data from phase III trials and real-world studies, with a focus on treatment outcomes in diverse populations.Expert opinion: BIC/FTC/TAF's high genetic barrier to resistance and independence from boosting agents represent strengths from the pharmacokinetic perspective. The combination's once-daily, single-tablet regimen ensures consistent therapeutic drug levels and makes this regimen a viable treatment choice even for those with suboptimal adherence. With clinical trial data demonstrating efficacy and safety, as well as ease of use, BIC/FTC/TAF plays a central role in international guidelines. As the HIV treatment landscape continues to evolve, this regimen will remain a cornerstone of oral ART and may serve as a model for future therapies.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635044","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

Clinical pharmacokinetics of levodopa and relevant add-on therapies for Parkinson's disease. 治疗帕金森病的左旋多巴和相关附加疗法的临床药代动力学。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-11-11 DOI: 10.1080/17425255.2024.2428831

Thomas Müller

{"title":"Clinical pharmacokinetics of levodopa and relevant add-on therapies for Parkinson's disease.","authors":"Thomas Müller","doi":"10.1080/17425255.2024.2428831","DOIUrl":"https://doi.org/10.1080/17425255.2024.2428831","url":null,"abstract":"Introduction: Parkinson's disease is a chronic neurodegenerative disease entity characterized by heterogeneity of symptoms and progression. Levodopa is an efficacious and well tolerated dopamine substituting drug for its therapy. Its O-methylation and generation of 3-O-methyldopa is enhanced by levodopa/dopa decarboxylase inhibitor formulations. Additional inhibition of catechol-O-methyltransferase is the relevant add on therapy for levodopa application. This pharmacologic approach increases the plasma appearance of levodopa and reduces 3-O-methyldopa synthesis. Available marketed compounds are entacapone, tolcapone and opicapone. Data on their effects on levodopa pharmacokinetics in patients are rare.Areas covered: This review describes the impact of this add-on therapy on the pharmacokinetic profile of levodopa and 3-O-methyldopa in plasma. The rationale was to perform a comparison with data from previously published pharmacokinetic trials with a standardized one time intake of levodopa/carbidopa without and with the available catechol-O-methyltransferase inhibitors.Expert opinion: Results of this analysis identified opicapone as the most efficacious inhibitor of catechol-O-methyltransferase in terms of changes of levodopa plasma concentrations. Opicapone induced higher levodopa plasma levels compared with the ones following application of levodopa/carbidopa alone or combined with entacapone or tolcapone. Co-administration of opicapone with its once daily intake regimen may support the efficacy of subcutaneous and intrajejunal levodopa infusions.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635042","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

In vitro neurotoxicity testing: lessons from chemotherapy-induced peripheral neurotoxicity. 体外神经毒性测试：从化疗引起的外周神经毒性中汲取教训。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-11-01 Epub Date: 2024-09-10 DOI: 10.1080/17425255.2024.2401584

Olga Tarasiuk, Chiara Invernizzi, Paola Alberti

{"title":"In vitro neurotoxicity testing: lessons from chemotherapy-induced peripheral neurotoxicity.","authors":"Olga Tarasiuk, Chiara Invernizzi, Paola Alberti","doi":"10.1080/17425255.2024.2401584","DOIUrl":"10.1080/17425255.2024.2401584","url":null,"abstract":"Introduction: Chemotherapy induced peripheral neurotoxicity (CIPN) is a long-lasting, or even permanent, late toxicity caused by largely used anticancer drugs. CIPN affects a growing population of cancer survivors and diminishes their quality of life since there is no curative/preventive treatment. Among several reasons for this unmet clinical need, there is an incomplete knowledge on mechanisms leading to CIPN. Therefore, bench side research is still greatly needed: in vitro studies are pivotal to both evaluate neurotoxicity mechanisms and potential neuroprotection strategies.Areas covered: Advantages and disadvantages of in vitro approaches are addressed with respect to their applicability to the CIPN field. Different cell cultures and techniques to assess neurotoxicity/neuroprotection are described. PubMed search-string: (chemotherapy-induced) AND (((neuropathy) OR neurotoxicity) OR neuropathic pain) AND (in vitro) AND (((((model) OR SH-SY5Y) OR PC12) OR iPSC) OR DRG neurons); (chemotherapy-induced) AND (((neuropathy) OR neurotoxicity) OR neuropathic pain) AND (model) AND (((neurite elongation) OR cell viability) OR morphology). No articles published before 1990 were selected.Expert opinion: CIPN is an ideal experimental setting to test axonal damage and, in general, peripheral nervous system mechanisms of disease and neuroprotection. Therefore, starting from robust preclinical data in this field, potentially, relevant biological rationale can be transferred to other human spontaneous diseases of the peripheral nervous system.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"1037-1052"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142157044","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

Analgesic medication considerations for chronic pain management post-bariatric surgery. 减肥手术后慢性疼痛治疗的镇痛药物注意事项。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-10-01 Epub Date: 2024-09-10 DOI: 10.1080/17425255.2024.2398631

Sumani Vij, Adriana Too, Victor Tsang, Denise Kreutzwiser

{"title":"Analgesic medication considerations for chronic pain management post-bariatric surgery.","authors":"Sumani Vij, Adriana Too, Victor Tsang, Denise Kreutzwiser","doi":"10.1080/17425255.2024.2398631","DOIUrl":"10.1080/17425255.2024.2398631","url":null,"abstract":"Introduction: Bariatric surgery, an option for obesity management, can significantly alter gastrointestinal structure and processes. These changes can impact the pharmacokinetics (PK) of medications, which can translate to clinical differences in efficacy and safety. Chronic pain is prevalent in obesity and often persists post-bariatric surgery.Areas covered: This narrative review examines the PubMed literature from 1990 to January 2024 for the impact of bariatric surgery on the management of chronic pain medications including non-opioid (acetaminophen, non-steroidal anti-inflammatory drugs, antidepressants, and cannabinoids) and opioid medications.Expert opinion: An individualized medication management approach is ideal for post-bariatric surgery patients, as PK parameters, type of surgery, time since surgery, and patient-specific factors make it difficult to support blanket recommendations. Close monitoring of efficacy and safety outcomes is essential in chronic pain management. While the PK of acetaminophen and opioids are impacted, the value of these medications in the setting of chronic pain is dwindling as more efficacy and safety data emerges. A life-long ban of NSAIDs due to marginal ulcer risk is not endorsed; rather, we advocate for shifting the focus to marginal ulcer prevention strategies, individualized benefit-risk analysis, and safety monitoring using surrogate markers.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"967-976"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082977","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

Analysis of drug-drug interactions in patients with HIV and metabolic syndrome. 艾滋病毒和代谢综合征患者的药物相互作用分析。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-10-01 Epub Date: 2024-09-10 DOI: 10.1080/17425255.2024.2401044

Jessica Tuan, Grace Igiraneza, Onyema Ogbuagu

{"title":"Analysis of drug-drug interactions in patients with HIV and metabolic syndrome.","authors":"Jessica Tuan, Grace Igiraneza, Onyema Ogbuagu","doi":"10.1080/17425255.2024.2401044","DOIUrl":"10.1080/17425255.2024.2401044","url":null,"abstract":"Background: People with HIV (PWH) are living longer directly related to benefits of highly effective antiretroviral therapy (ART). However, concurrent with improved longevity is the growing prevalence of metabolic comorbidities that drive morbidity and mortality among PWH. There is an increasing repertoire of treatment options for metabolic disorders. Thus, it is important for clinicians to understand the drug-drug interactions (DDIs) between ART and treatments for metabolic disorders.Areas covered: This review will discuss DDIs between contemporary ART and agents used to treat metabolic syndrome (diabetes, dyslipidemia, obesity and hypertension). Literature review of published and unpublished data from manuscripts, conference proceedings, regulatory submissions, and drug prescribing information were conducted from the following sources: PubMed, Google, and Google Scholar through January 2024.Expert opinion: People with HIV have a high prevalence of metabolic disorders. Most significant DDIs between ART and treatments for metabolic disorders are unidirectional with ART as perpetrators, rather than victims, such that careful selection of ART with low DDI propensity can address the concern. However, there are data gaps with DDI data for long-acting ART as well as newer oral and injectable medications for diabetes and weight loss. Nanotechnology-based drug delivery platforms hold promise to address some problematic DDIs.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"953-965"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127744","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

Clinical pharmacokinetics of cefpodoxime: a systematic review. 头孢泊肟的临床药代动力学：系统综述。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-10-01 Epub Date: 2024-08-13 DOI: 10.1080/17425255.2024.2391389

Ayesha Farooq, Ammara Zamir, Imran Imran, Hamid Saeed, Faleh Alqahtani, Anees Ur Rehman, Waseem Ashraf, Muhammad Fawad Rasool

{"title":"Clinical pharmacokinetics of cefpodoxime: a systematic review.","authors":"Ayesha Farooq, Ammara Zamir, Imran Imran, Hamid Saeed, Faleh Alqahtani, Anees Ur Rehman, Waseem Ashraf, Muhammad Fawad Rasool","doi":"10.1080/17425255.2024.2391389","DOIUrl":"10.1080/17425255.2024.2391389","url":null,"abstract":"Introduction: Cefpodoxime, a third-generation cephalosporin, is a broad-spectrum antibiotic widely used to treat acute upper respiratory tract infections (RTI). This systematic review aims to present a comprehensive view of all the available pharmacokinetics (PK) data associated with the pharmacodynamics (PD) parameters of cefpodoxime in humans.Areas covered: The PubMed, Google Scholar, Cochrane Library, and Science Direct, were systematically searched to identify studies on the PK of cefpodoxime. Out of 746 papers, 26 articles meeting the eligibility criteria were included that have reported the PK data. The drug exposure for the patients undergoing hemodialysis was 50% lower than healthy participants. The renal clearance was almost 27% less in pediatric patients than in adults. The plasma concentrations of cefpodoxime exceeded the minimum inhibitory concentration (MIC) for 90% of skin pathogens, including Streptococcus species and Staphylococcus species (i.e.) < 1 μg/mL and 2-4 μg/mL respectively.Expert opinion: The current study includes detailed information on clinical PK of cefpodoxime in healthy, diseased, pediatric populations as well as drug-drug interactions and drug-food interactions. Moreover, this systematic review also explicated PK/PD properties of drug with a specific impact on MIC of drug. The present review will also assist clinicians in the development of PK models for cefpodoxime.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"989-1001"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908626","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

Underlying mechanisms and management strategies for regorafenib-induced toxicity in hepatocellular carcinoma. 肝细胞癌中瑞戈非尼诱发毒性的基本机制和管理策略。

Expert opinion on drug metabolism & toxicology Pub Date : 2024-09-01 Epub Date: 2024-09-03 DOI: 10.1080/17425255.2024.2398628

Mengting Cheng, Xinyu Tao, Fei Wang, Nonger Shen, Zhifei Xu, Yuhuai Hu, Ping Huang, Peihua Luo, Qiaojun He, Yiwen Zhang, Fangjie Yan

{"title":"Underlying mechanisms and management strategies for regorafenib-induced toxicity in hepatocellular carcinoma.","authors":"Mengting Cheng, Xinyu Tao, Fei Wang, Nonger Shen, Zhifei Xu, Yuhuai Hu, Ping Huang, Peihua Luo, Qiaojun He, Yiwen Zhang, Fangjie Yan","doi":"10.1080/17425255.2024.2398628","DOIUrl":"10.1080/17425255.2024.2398628","url":null,"abstract":"Introduction: Hepatocellular carcinoma (HCC) accounts for 85% of liver cancer cases and is the third leading cause of cancer death. Regorafenib is a multi-target inhibitor that dramatically prolongs progression-free survival in HCC patients who have failed sorafenib therapy. However, one of the primary factors limiting regorafenib's clinical utilization is toxicity. Using Clinical Trials.gov and PubMed, we gathered clinical data on regorafenib and conducted a extensive analysis of the medication's adverse reactions and mechanisms. Next, we suggested suitable management techniques to improve regorafenib's effectiveness.Areas covered: We have reviewed the mechanisms by which regorafenib-induced toxicity occurs and general management strategies through clinical trials of regorafenib. Furthermore, by examining the literature on regorafenib and other tyrosine kinase inhibition, we summarized the mechanics of the onset of regorafenib toxicity and mechanism-based intervention strategies by reviewing the literature related to regorafenib and other tyrosine kinase inhibition.Expert opinion: One of the primary factors restricting regorafenib's clinical utilization and combination therapy is its toxicity reactions. To optimize regorafenib treatment regimens, it is especially important to further understand the specific toxicity mechanisms of regorafenib as a multi-kinase inhibitor.","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"907-922"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121425","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