Expert Opinion on Drug Metabolism & Toxicology最新文献_第3页

Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach. 优化用于治疗骨关节感染的抗菌治疗的药代动力学和药效学考虑因素：一种基于证据的算法方法。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-09-14 DOI: 10.1080/17425255.2023.2255525

Milo Gatti, Sara Tedeschi, Eleonora Zamparini, Federico Pea, Pierluigi Viale

{"title":"Pharmacokinetic and pharmacodynamic considerations for optimizing antimicrobial therapy used to treat bone and joint infections: an evidence-based algorithmic approach.","authors":"Milo Gatti, Sara Tedeschi, Eleonora Zamparini, Federico Pea, Pierluigi Viale","doi":"10.1080/17425255.2023.2255525","DOIUrl":"10.1080/17425255.2023.2255525","url":null,"abstract":"Introduction: Bone and joint infections (BJIs) are a major health concern causing remarkable morbidity and mortality. However, which antimicrobial treatment could be the best according to specific clinical scenarios and/or to the pharmacokinetic/pharmacodynamic (PK/PD) features remains an unmet clinical need. This multidisciplinary opinion article aims to develop evidence-based algorithms for empirical and targeted antibiotic therapy of patients affected by BJIs.Areas covered: A multidisciplinary team of four experts had several rounds of assessment for developing algorithms devoted to empirical and targeted antimicrobial therapy of BJIs. A literature search was performed on PubMed-MEDLINE (until April 2023) to provide evidence for supporting therapeutic choices. Four different clinical scenarios were structured according to specific infection types (i.e. vertebral osteomyelitis, prosthetic joint infections, infected non-unions and other chronic osteomyelitis, and infectious arthritis), need or not of surgical intervention or revision, isolation or not of clinically relevant bacterial pathogens from blood and/or tissue cultures, and PK/PD features of antibiotics.Expert opinion: The proposed therapeutic algorithms were based on a multifaceted approach considering the peculiar features of each antibiotic (spectrum of activity, PK/PD properties, bone penetration rate, and anti-biofilm activity), and could be hopefully helpful in improving clinical outcome of BJIs.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"511-535"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic, toxicological, and clinical considerations for the treatment of type 2 diabetes in patients with liver disease: a comprehensive update. 肝病患者治疗2型糖尿病的药代动力学、毒理学和临床注意事项：全面更新。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-08-29 DOI: 10.1080/17425255.2023.2252333

André J Scheen

{"title":"Pharmacokinetic, toxicological, and clinical considerations for the treatment of type 2 diabetes in patients with liver disease: a comprehensive update.","authors":"André J Scheen","doi":"10.1080/17425255.2023.2252333","DOIUrl":"10.1080/17425255.2023.2252333","url":null,"abstract":"Introduction: Type 2 diabetes and liver disease, mainly metabolic-associated fatty liver disease (MAFLD) and more rarely cirrhosis, coexist in many patients. This duality has direct implications for the physician when choosing glucose-lowering agents, with classical concerns but also recent new hopes.Areas covered: This updated comprehensive review will consider the pharmacokinetics, the tolerance/safety profile, the benefit/risk balance in cirrhosis, the effects on MAFLD and the risk of hepatocellular carcinoma of old and new glucose-lowering compounds in patients with liver disease, with a special focus on glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors.Expert opinion: We are currently facing a new paradigm in the management of patients with diabetes and liver disease. From previous reluctance when using antidiabetic agents (except insulin) in diabetic patients with hepatic impairment because of safety concerns, the commercialization of novel glucose-lowering agents has changed the scene. These agents, which have a good safety profile, are associated with weight loss and pleiotropic effects. They have proven their efficacy in improving MAFLD. However, more specific studies are still needed to prove their efficacy in preventing the progression to fibrosis/cirrhosis and confirm this new opportunity for the management of patients with diabetes and liver disease.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"543-553"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10477527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Clinical pharmacokinetics of antipsychotics in pediatric populations: a scoping review focusing on dosing regimen. 抗精神病药物在儿科人群中的临床药代动力学：一项以给药方案为重点的范围综述。

IF 3.9 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-09-12 DOI: 10.1080/17425255.2023.2252340

Jiayi Liang, Lisa T Ringeling, Rebecca A Hermans, Izgi Bayraktar, Tessa M Bosch, Karin M Egberts, Sanne M Kloosterboer, Brenda de Winter, Bram Dierckx, Birgit C P Koch

{"title":"Clinical pharmacokinetics of antipsychotics in pediatric populations: a scoping review focusing on dosing regimen.","authors":"Jiayi Liang, Lisa T Ringeling, Rebecca A Hermans, Izgi Bayraktar, Tessa M Bosch, Karin M Egberts, Sanne M Kloosterboer, Brenda de Winter, Bram Dierckx, Birgit C P Koch","doi":"10.1080/17425255.2023.2252340","DOIUrl":"10.1080/17425255.2023.2252340","url":null,"abstract":"Introduction: Achieving optimal clinical responses and minimizing side effects through precision dosing of antipsychotics in children and adolescents with psychiatric disorders remains a challenge. Identifying patient characteristics (covariates) that affect pharmacokinetics can inform more effective dosing strategies and ultimately improve patient outcomes. This review aims to provide greater insight into the impact of covariates on the clinical pharmacokinetics of antipsychotics in pediatric populations.Areas covered: A comprehensive literature search was conducted, and the main findings regarding the effects of the covariates on the pharmacokinetics of antipsychotics in children and adolescents are presented.Expert opinion: Our study highlights significant covariates, including age, sex, weight, CYP2D6 phenotype, co-medication, and smoking habits, which affect the pharmacokinetics of antipsychotics. However, the findings were generally limited by the small sample sizes of naturalistic, open-label, observational studies, and the homogeneous subgroups. Dosing based on weight and preemptive genotyping could prove beneficial for optimizing the dosing regimen in pediatric populations. Future research is needed to refine dosing recommendations and establish therapeutic reference ranges critical for precision dosing and Therapeutic Drug Monitoring (TDM). The integration of individual patient characteristics with TDM can further optimize the efficacy and safety of antipsychotics for each patient.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"501-509"},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10211284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Individualized dosing algorithms for tacrolimus in kidney transplant recipients: current status and unmet needs. 肾移植受者他克莫司的个性化给药算法：现状和未满足的需求。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-08-29 DOI: 10.1080/17425255.2023.2250251

Maaike R Schagen, Helena Volarevic, Marith I Francke, Sebastiaan D T Sassen, Marlies E J Reinders, Dennis A Hesselink, Brenda C M de Winter

{"title":"Individualized dosing algorithms for tacrolimus in kidney transplant recipients: current status and unmet needs.","authors":"Maaike R Schagen, Helena Volarevic, Marith I Francke, Sebastiaan D T Sassen, Marlies E J Reinders, Dennis A Hesselink, Brenda C M de Winter","doi":"10.1080/17425255.2023.2250251","DOIUrl":"10.1080/17425255.2023.2250251","url":null,"abstract":"Introduction: Tacrolimus is a potent immunosuppressive drug with many side effects including nephrotoxicity and post-transplant diabetes mellitus. To limit its toxicity, therapeutic drug monitoring (TDM) is performed. However, tacrolimus' pharmacokinetics are highly variable within and between individuals, which complicates their clinical management. Despite TDM, many kidney transplant recipients will experience under- or overexposure to tacrolimus. Therefore, dosing algorithms have been developed to limit the time a patient is exposed to off-target concentrations.Areas covered: Tacrolimus starting dose algorithms and models for follow-up doses developed and/or tested since 2015, encompassing both adult and pediatric populations. Literature was searched in different databases, i.e. Embase, PubMed, Web of Science, Cochrane Register, and Google Scholar, from inception to February 2023.Expert opinion: Many algorithms have been developed, but few have been prospectively evaluated. These performed better than bodyweight-based starting doses, regarding the time a patient is exposed to off-target tacrolimus concentrations. No benefit in reduced tacrolimus toxicity has yet been observed. Most algorithms were developed from small datasets, contained only a few tacrolimus concentrations per person, and were not externally validated. Moreover, other matrices should be considered which might better correlate with tacrolimus toxicity than the whole-blood concentration, e.g. unbound plasma or intra-lymphocytic tacrolimus concentrations.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"429-445"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10114231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects. 钠-葡萄糖协同转运蛋白2抑制剂DWP16001与苯妥明在健康受试者中的药代动力学和药效学相互作用。

IF 3.9 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-08-25 DOI: 10.1080/17425255.2023.2249397

Sukyong Yoon, Min Soo Park, Byung Hak Jin, Hyobin Shin, Jaejin Na, Wan Huh, Choon Ok Kim

{"title":"Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects.","authors":"Sukyong Yoon, Min Soo Park, Byung Hak Jin, Hyobin Shin, Jaejin Na, Wan Huh, Choon Ok Kim","doi":"10.1080/17425255.2023.2249397","DOIUrl":"10.1080/17425255.2023.2249397","url":null,"abstract":"Background: DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine.Methods: We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD.Results: The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of Cmax,ss, and AUCtau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance.Conclusions: Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes.Clinical trial registration: NCT05321732.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"479-485"},"PeriodicalIF":3.9,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10066815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A comprehensive update of hormone-related pharmacokinetic variations associated with breast cancer drugs. 与乳腺癌症药物相关的激素相关药代动力学变化的全面更新。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-09-11 DOI: 10.1080/17425255.2023.2244870

Luca Boscolo Bielo, Stefano Natangelo, Jalissa Katrini, Dario Trapani, Giuseppe Curigliano

{"title":"A comprehensive update of hormone-related pharmacokinetic variations associated with breast cancer drugs.","authors":"Luca Boscolo Bielo, Stefano Natangelo, Jalissa Katrini, Dario Trapani, Giuseppe Curigliano","doi":"10.1080/17425255.2023.2244870","DOIUrl":"10.1080/17425255.2023.2244870","url":null,"abstract":"Introduction: Drugs available for the treatment of breast cancer are increasing, yielding improved oncological outcomes. The efficacy and safety of anticancer drugs significantly depend on pharmacokinetic profiles, which could be influenced by several factors, such as sex hormones.Areas covered: This article discusses the potential hormone-related pharmacokinetic influences on novel breast cancer pharmacotherapies.Expert opinion: Recently approved drugs for the treatment of breast cancer belong to different classes, each with unique pharmacokinetic profile. The impact of hormones, such as estrogen and progesterone, may occur at different steps of drug metabolism. Key effects of sex hormones ha ve been reported on multidrug-resistant transporters and enzymes involved in the liver metabolism of drugs, such as cytochromes. Nevertheless, no data is currently available to establish hormone-related metabolic interactions that may account for variability in drug scheduling and selection. Whereas we recognize influences may occur, we do not assume hormones alone can yield clinically significant metabolic changes. Rather, we believe that hormonal influences should be considered along with other elements that may affect drugs metabolism, such as concomitant medications, age-related pharmacokinetic changes, and genetic polymorphisms, in order to deliver treatment personalization and ensure better tolerability and safety of anticancer treatments.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"389-403"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10212846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current state-of-the-art approaches for mass spectrometry in clinical toxicology: an overview. 当前最先进的质谱法在临床毒理学中的应用：综述。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-09-01 DOI: 10.1080/17425255.2023.2252324

Frank T Peters, Daniela Wissenbach

{"title":"Current state-of-the-art approaches for mass spectrometry in clinical toxicology: an overview.","authors":"Frank T Peters, Daniela Wissenbach","doi":"10.1080/17425255.2023.2252324","DOIUrl":"10.1080/17425255.2023.2252324","url":null,"abstract":"Introduction: Hyphenated mass spectrometry (MS) has evolved into a very powerful analytical technique of high sensitivity and specificity. It is used to analyze a very wide spectrum of analytes in classical and alternative matrices. The presented paper will provide an overview of the current state-of-the-art of hyphenated MS applications in clinical toxicology primarily based on review articles indexed in PubMed (1990 to April 2023).Areas covered: A general overview of matrices, sample preparation, analytical systems, detection modes, and validation and quality control is given. Moreover, selected applications are discussed.Expert opinion: A more widespread use of hyphenated MS techniques, especially in systematic toxicological analysis and drugs of abuse testing, would help overcome limitations of immunoassay-based screening strategies. This is currently hampered by high instrument cost, qualification requirements for personnel, and less favorable turnaround times, which could be overcome by more user-friendly, ideally fully automated MS instruments. This would help making hyphenated MS-based analysis available in more laboratories and expanding analysis to a large number of organic drugs, poisons, and/or metabolites. Even the most recent novel psychoactive substances (NPS) could be presumptively identified by high-resolution MS methods, their likely presence be communicated to treating physicians, and be confirmed later on.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"487-500"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A comprehensive update of the metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation. 胰腺移植过程中使用的免疫抑制药物的代谢和毒理学考虑因素的全面更新。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-08-09 DOI: 10.1080/17425255.2023.2243808

Ana Cláudia Vidigal, Débora D de Lucena, Stephany Beyerstedt, Érika B Rangel

{"title":"A comprehensive update of the metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation.","authors":"Ana Cláudia Vidigal, Débora D de Lucena, Stephany Beyerstedt, Érika B Rangel","doi":"10.1080/17425255.2023.2243808","DOIUrl":"10.1080/17425255.2023.2243808","url":null,"abstract":"Introduction: Despite significant advancements in immunosuppressive regimens and surgical techniques, the prevalence of adverse events related to immunosuppression remains a major challenge affecting the long-term survival rates of pancreas and kidney allografts.Areas covered: This article presents a comprehensive review of the literature and knowledge (Jan/2012-Feb/2023) concerning glucose metabolism disorders and nephrotoxicity associated with tacrolimus and mammalian target of rapamycin inhibitors (mTORi). Novel signaling pathways potentially implicated in these adverse events are discussed. Furthermore, we extensively examine the findings from clinical trials evaluating the efficacy and safety of tacrolimus, mTORi, and steroid minimization.Expert opinion: Tacrolimus-based regimens continue to be the standard treatment following pancreas transplants. However, prolonged use of tacrolimus and mTORi may lead to hyperglycemia and nephrotoxicity. Understanding and interpreting experimental data, particularly concerning novel signaling pathways beyond calcineurin-NFAT and mTOR pathways, can offer valuable insights for therapeutic interventions to mitigate hyperglycemia and nephrotoxicity. Additionally, critically analyzing clinical trial results can identify opportunities for personalized safety-based approaches to minimize side effects. It is imperative to conduct randomized-controlled studies to assess the impact of mTORi use and steroid-free protocols on pancreatic allograft survival. Such studies will aid in tailoring treatment strategies for improved transplant outcomes.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"405-427"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A randomized, single-blind, single-dose, parallel-group study in healthy subjects to demonstrate the pharmacokinetic equivalence of trastuzumab and its biosimilar. 在健康受试者中进行随机、单盲、单剂量、平行组研究，以证明曲妥珠单抗及其生物类似药的药代动力学等效性。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-08-03 DOI: 10.1080/17425255.2023.2243823

Yanli Wang, Zhengzhi Liu, Qiaohuan Deng, Zhengjie Su, Jinling Xue, Yicheng Zhao, Haimiao Yang

{"title":"A randomized, single-blind, single-dose, parallel-group study in healthy subjects to demonstrate the pharmacokinetic equivalence of trastuzumab and its biosimilar.","authors":"Yanli Wang, Zhengzhi Liu, Qiaohuan Deng, Zhengjie Su, Jinling Xue, Yicheng Zhao, Haimiao Yang","doi":"10.1080/17425255.2023.2243823","DOIUrl":"10.1080/17425255.2023.2243823","url":null,"abstract":"Background: Trastuzumab is a humanized anti-HER2 monoclonal antibody used in the treatment of breast cancer. This study compared the pharmacokinetics (PK), immunogenicity and safety of trastuzumab (Roche Pharma AG) and its biosimilar (Chia Tai Tianqing Pharmaceutical Group Co. Ltd) in healthy Chinese subjects.Research design and methods: A randomized, parallel, double-blind, single-dose study was conducted. Healthy male subjects were randomized to receive trastuzumab (n = 43) or its biosimilar (n = 43) intravenously at a dose of 4 mg. Plasma drug concentrations were detected by enzyme-linked immunosorbent assay (ELISA), and PK parameters were statistically analyzed. Safety and immunogenicity were also evaluated.Results: The geometric mean ratios (GMRs) of AUC0-t, Cmax and AUC0-∞ for trastuzumab and its biosimilar were 92.3%, 100.77% and 92.2%, respectively. The 90% CIs were all within 80%-125%, meeting the bioequivalence standards. No serious adverse events or immunogenicity were reported, and all the adverse events reported were mild and similar between the two treatment groups.Conclusions: Trastuzumab was well tolerated, showed a similar safety profile to its biosimilar, and demonstrated PK equivalence.Clinical trial registration: This trial was registered at the [anonymized].","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"849-855"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potential drug-drug interactions with mitogen-activated protein kinase (MEK) inhibitors used to treat melanoma. 与用于治疗黑色素瘤的丝裂原活化蛋白激酶（MEK）抑制剂的潜在药物相互作用。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-07-01 Epub Date: 2023-09-06 DOI: 10.1080/17425255.2023.2255519

A Marani, H Gioacchini, M Paolinelli, A Offidani, A Campanati

{"title":"Potential drug-drug interactions with mitogen-activated protein kinase (MEK) inhibitors used to treat melanoma.","authors":"A Marani, H Gioacchini, M Paolinelli, A Offidani, A Campanati","doi":"10.1080/17425255.2023.2255519","DOIUrl":"10.1080/17425255.2023.2255519","url":null,"abstract":"Introduction: The management of patients with BRAF-mutated advanced melanoma who are undergoing targeted therapy with MEK inhibitors can be complicated by the co-administration of multiple medications, which can give rise to drug-drug interactions of clinical significance.Covered areas: Our review presents a comprehensive analysis of the pharmacokinetic and pharmacodynamic interactions of the three approved for advanced melanoma MEK inhibitor drugs - binimetinib, cobimetinib, and trametinib. MEDLINE (PubMed) was utilized for the literature search, comprising clinical studies, observational studies, and preclinical research. The review discusses the impact of these interactions on efficacy and safety of the treatments and differentiates between interactions supported by pharmacokinetic or pharmacodynamic mechanisms, those encountered in clinical practice, and those observed in preclinical studies.Expert opinion: Physicians should be aware about potential benefits, but also increased toxicity caused by drug interactions between MEK inhibitors and other drugs in the management of patients with metastatic melanoma.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"555-567"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10163278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0