Expert Opinion on Drug Metabolism & Toxicology最新文献_第9页

A review on the clinical pharmacokinetics of hydralazine. 肼嗪的临床药动学研究进展。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-10-01 Epub Date: 2022-09-27 DOI: 10.1080/17425255.2022.2129005

Asma Shahzad Qamar, Ammara Zamir, Sundus Khalid, Waseem Ashraf, Imran Imran, Iltaf Hussain, Anees Ur Rehman, Hamid Saeed, Abdul Majeed, Faleh Alqahtani, Muhammad Fawad Rasool

{"title":"A review on the clinical pharmacokinetics of hydralazine.","authors":"Asma Shahzad Qamar, Ammara Zamir, Sundus Khalid, Waseem Ashraf, Imran Imran, Iltaf Hussain, Anees Ur Rehman, Hamid Saeed, Abdul Majeed, Faleh Alqahtani, Muhammad Fawad Rasool","doi":"10.1080/17425255.2022.2129005","DOIUrl":"https://doi.org/10.1080/17425255.2022.2129005","url":null,"abstract":"Introduction: Hydralazine is a vasodilator used to treat hypertension, pre-eclampsia, and heart failure. The current article reviews the clinical pharmacokinetics (PK) of hydralazine, which can be useful for clinicians in optimizing its dose and dosing frequency to avoid adverse effects and unexpected interactions that could risk patients' lives.Areas covered: This review has summarized the PK parameters for hydralazine after performing an extensive literature search. It includes 20 publications that were selected after applying eligibility criteria out of a pool of literature that was searched using Google Scholar, PubMed, Cochrane Central, and EBSCO databases. The included studies consisted of concentration vs. time profiles of hydralazine. If the PK data were not tabulated in the given study, the concentration vs. time profiles were scanned for the extraction of the PK data. The PK parameters were calculated by applying a non-compartmental analysis (NCA).Expert opinion: The current review will aid clinicians in understanding hydralazine PK in different disease populations. This clinical PK data might also be helpful in the development of a pharmacokinetic model of hydralazine.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 10","pages":"707-714"},"PeriodicalIF":4.3,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33479850","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: 4

Drug pharmacokinetics in the obese population: challenging common assumptions on predictors of obesity-related parameter changes. 肥胖人群的药物药代动力学:挑战肥胖相关参数变化预测因子的常见假设。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-10-01 Epub Date: 2022-10-20 DOI: 10.1080/17425255.2022.2132931

Tan Zhang, Elke H J Krekels, Cornelis Smit, Catherijne A J Knibbe

{"title":"Drug pharmacokinetics in the obese population: challenging common assumptions on predictors of obesity-related parameter changes.","authors":"Tan Zhang, Elke H J Krekels, Cornelis Smit, Catherijne A J Knibbe","doi":"10.1080/17425255.2022.2132931","DOIUrl":"https://doi.org/10.1080/17425255.2022.2132931","url":null,"abstract":"Introduction: Obesity is associated with many physiological changes. We review available evidence regarding five commonly accepted assumptions to a priori predict the impact of obesity on drug pharmacokinetics (PK).Areas covered: The investigated assumptions are: 1) lean body weight is the preferred descriptor of clearance and dose adjustments; 2) volume of distribution increases for lipophilic, but not for hydrophilic drugs; 3) CYP-3A4 activity is suppressed and UGT activity is increased, implying decreased and increased dose requirements for substrates of these enzyme systems, respectively; 4) glomerular filtration rate is enhanced, necessitating higher doses for drugs cleared through glomerular filtration; 5) drug dosing information from obese adults can be extrapolated to obese adolescents.Expert opinion: Available literature contradicts, or at least limits the generalizability, of all five assumptions. Clinical studies should focus on quantifying the impact of duration and severity of obesity on drug PK in adults and adolescents, and also include oral bioavailability and pharmacodynamics in these studies. Physiologically based PK approaches can be used to predict PK changes for individual drugs but can also be used to define in general terms based on patient characteristics and drug properties, when certain assumptions can or cannot be expected to be systematically accurate.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 10","pages":"657-674"},"PeriodicalIF":4.3,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33499104","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: 13

Biology and therapeutic applications of the proton-coupled folate transporter. 质子偶联叶酸转运蛋白的生物学和治疗应用。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-10-01 Epub Date: 2022-10-20 DOI: 10.1080/17425255.2022.2136071

Larry H Matherly, Mathew Schneider, Aleem Gangjee, Zhanjun Hou

{"title":"Biology and therapeutic applications of the proton-coupled folate transporter.","authors":"Larry H Matherly, Mathew Schneider, Aleem Gangjee, Zhanjun Hou","doi":"10.1080/17425255.2022.2136071","DOIUrl":"10.1080/17425255.2022.2136071","url":null,"abstract":"Introduction: The proton-coupled folate transporter (PCFT; SLC46A1) was discovered in 2006 as the principal mechanism by which folates are absorbed in the intestine and the causal basis for hereditary folate malabsorption (HFM). In 2011, it was found that PCFT is highly expressed in many tumors. This stimulated interest in using PCFT for cytotoxic drug targeting, taking advantage of the substantial levels of PCFT transport and acidic pH conditions commonly associated with tumors.Areas covered: We summarize the literature from 2006 to 2022 that explores the role of PCFT in the intestinal absorption of dietary folates and its role in HFM and as a transporter of folates and antifolates such as pemetrexed (Alimta) in relation to cancer. We provide the rationale for the discovery of a new generation of targeted pyrrolo[2,3-d]pyrimidine antifolates with selective PCFT transport and inhibitory activity toward de novo purine biosynthesis in solid tumors. We summarize the benefits of this approach to cancer therapy and exciting new developments in the structural biology of PCFT and its potential to foster refinement of active structures of PCFT-targeted anti-cancer drugs.Expert opinion: We summarize the promising future and potential challenges of implementing PCFT-targeted therapeutics for HFM and a variety of cancers.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 10","pages":"695-706"},"PeriodicalIF":4.3,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

The mysteries of target site concentrations of antibiotics in bone and joint infections: what is known? A narrative review. 骨关节感染中抗生素靶位浓度的奥秘:我们知道什么?叙述性评论

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-09-01 Epub Date: 2022-09-04 DOI: 10.1080/17425255.2022.2117607

Birgit C P Koch, Qiaolin Zhao, Maartje Oosterhoff, Jakob van Oldenrijk, Alan Abdulla, Brenda C M de Winter, Koen Bos, Anouk E Muller

{"title":"The mysteries of target site concentrations of antibiotics in bone and joint infections: what is known? A narrative review.","authors":"Birgit C P Koch, Qiaolin Zhao, Maartje Oosterhoff, Jakob van Oldenrijk, Alan Abdulla, Brenda C M de Winter, Koen Bos, Anouk E Muller","doi":"10.1080/17425255.2022.2117607","DOIUrl":"https://doi.org/10.1080/17425255.2022.2117607","url":null,"abstract":"Introduction: Currently, antibiotic treatment is often a standard dosing regimen in bone and joint infections (BJI). However, it remains unknown if exposure at the target-site is adequate. The aim of this review is to gain more insight in the relationship between the target site concentration of antibiotic and the minimal inhibitory concentration to target the bacteria in bone and joint infections (BJI).Areas covered: A literature search was performed by Erasmus MC Medical library. Bone, bone tissue and synovial concentration of antibiotics were covered in humans. In addition, we reported number of patients, dose, sampling method, analytical method and tissue and plasma concentrations. We used the epidemiological cutoff value (ECOFF) values of the targeted micro-organisms. If more than 3 publications were available on the antibiotic, we graphically presented ECOFFS values against reported antibiotic concentrations.Expert opinion: For most antibiotics, the literature is sparse. In addition, a lot of variable and total antibiotic concentrations are published. Ciprofloxacin, cefazolin, cefuroxime, vancomycin and linezolid seem to have adequate average exposure if correlating total concentration to ECOFF, when standard dosing is used. With regard to other antibiotics, results are inconclusive. More extensive pharmacokinetic/pharmacodynamic modeling in BJI is needed.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"587-600"},"PeriodicalIF":4.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40639764","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: 1

Treatment of non-metastatic castration-resistant prostate cancer: facing age-related comorbidities and drug-drug interactions. 非转移性去势抵抗性前列腺癌的治疗:面对年龄相关的合并症和药物-药物相互作用。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-09-01 Epub Date: 2022-09-16 DOI: 10.1080/17425255.2022.2122812

David Conde-Estévez, Iván Henríquez, Jesús Muñoz-Rodríguez, Alejo Rodriguez-Vida

{"title":"Treatment of non-metastatic castration-resistant prostate cancer: facing age-related comorbidities and drug-drug interactions.","authors":"David Conde-Estévez, Iván Henríquez, Jesús Muñoz-Rodríguez, Alejo Rodriguez-Vida","doi":"10.1080/17425255.2022.2122812","DOIUrl":"https://doi.org/10.1080/17425255.2022.2122812","url":null,"abstract":"Introduction: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) are frequently poly-medicated due to age-related and androgen deprivation therapy (ADT)-derived comorbidities. In high-risk patients, androgen receptor inhibitors (ARIs) have shown to delay disease progression; however, drug-drug interactions (DDIs) with preexisting medications may impact the therapeutic effect and safety of these and of the ARIs themselves.Areas covered: We review the potential comorbidity burden of nmCRPC patients on the basis of epidemiologic studies on age-related comorbidities, the impact of ADT and specific studies analyzing this topic. Using the DDIs compendia Lexicomp® and Drugs.com®, we provide a scenario of the potential DDIs between common mediations used to treat these comorbidities and the three currently available ARIs: apalutamide, enzalutamide and darolutamide.Expert opinion: In high-risk nmCRPC patients to be treated with an ARI, careful multidisciplinary evaluation of potential DDIs is a fundamental component in the clinical-decision making. The lower potential for DDIs, the lower need for dose adjustment or change of current comedications and of patient monitoring, and safer introduction of new comedications. To optimize this step, an effort is still needed to determine the clinical relevance of DDIs and to harmonize their definition and classification among the different compendia.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"601-613"},"PeriodicalIF":4.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40362368","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

Pharmacokinetic considerations surrounding the use of levetiracetam for seizure prophylaxis in neurocritical care - an overview. 在神经危重症患者中，左乙拉西坦用于癫痫预防的药代动力学研究综述。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-09-01 Epub Date: 2022-08-30 DOI: 10.1080/17425255.2022.2117606

Gianluca D'Onofrio, Antonella Riva, Elisabetta Amadori, Simona Lattanzi, Klaus Rose, Alberto Verrotti, Pasquale Striano

{"title":"Pharmacokinetic considerations surrounding the use of levetiracetam for seizure prophylaxis in neurocritical care - an overview.","authors":"Gianluca D'Onofrio, Antonella Riva, Elisabetta Amadori, Simona Lattanzi, Klaus Rose, Alberto Verrotti, Pasquale Striano","doi":"10.1080/17425255.2022.2117606","DOIUrl":"https://doi.org/10.1080/17425255.2022.2117606","url":null,"abstract":"Introduction: Levetiracetam (LEV) is one of the most widely used anti-seizure medications (ASMs) in clinical practice. This is due both to a different mechanism of action when compared to other ASMs and its easy handling. Indeed, because of its interesting pharmacokinetic properties, it is often used outside of the labeled indications, notably in the neurocritical setting as prophylaxis of epileptic seizures.Areas covered: A literature search was conducted and the most relevant studies on the pharmacokinetic properties of LEV were selected by two independent investigators. Current evidence on the use of ASM prophylaxis in the neurocritical setting was also reviewed, highlighting and discussing the strengths and limits of LEV as drug of choice for anti-epileptic prophylaxis in this scenario.Expert opinion: LEV has a 'near-ideal' pharmacokinetic profile, which makes it an attractive drug for ASM prophylaxis in neurocritical care. However, current recommendations restrict ASMs prophylaxis to very selected circumstances and the role of LEV is marginal. Moreover, studies are generally designed to compare LEV versus phenytoin, whereas studies comparing LEV versus placebo are lacking. Further, randomized trials will be needed to better elucidate LEV utility and its neuroprotective role in the neurocritical setting.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"575-585"},"PeriodicalIF":4.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40637351","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

Local anesthetics and erector spinae plane blocks: a spotlight on pharmacokinetic considerations and toxicity risks. 局部麻醉剂和竖脊肌平面阻滞:药物动力学考虑和毒性风险的焦点。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-09-01 Epub Date: 2022-09-22 DOI: 10.1080/17425255.2022.2122811

Alessandro De Cassai, Federico Geraldini, Fabio Costa, Serkan Tulgar

{"title":"Local anesthetics and erector spinae plane blocks: a spotlight on pharmacokinetic considerations and toxicity risks.","authors":"Alessandro De Cassai, Federico Geraldini, Fabio Costa, Serkan Tulgar","doi":"10.1080/17425255.2022.2122811","DOIUrl":"https://doi.org/10.1080/17425255.2022.2122811","url":null,"abstract":"The Erector Spinae Plane (ESP) block was first described in 2016 and from its inception it has attracted great interest from the scientific community related to anesthesia and pain practice [1]. It is performed by injecting a solution of local anesthetics (LA) in a virtual plane between the transverse processes and the erector spinae muscle group, with the anesthetic solution subsequently spreading for a variable number of vertebral levels (Figure 1). Understanding ESP block pharmacokinetics and related concerns requires two key points. Firstly, a successful ESP block relies on the use of large volumes of anesthetics. Given that the target is not a nerve or a small compartment but a virtual plane where the anesthetic spreads, large volumes are usually necessary to reach the desired effect. In literature, while the injected LA covers a median of one dermatome every 3.4 ml of solution, spread has been reported as being widely variable [2]. Secondly, the ESP is performed in a highly vascularized surface, as on the erector spinae muscle group lies a rich vascular bed [3,4]. Given the above, it is of foremost importance to evaluate the pharmacokinetics of the drugs injected in the ESP to evaluate the possibility of local anesthetic systemic toxicity (LAST).","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 9","pages":"537-539"},"PeriodicalIF":4.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455961","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: 3

Modeling drug-induced liver injury: current status and future prospects. 药物性肝损伤模型:现状与展望。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-09-01 Epub Date: 2022-09-16 DOI: 10.1080/17425255.2022.2122810

Daniel E Di Zeo-Sánchez, Antonio Segovia-Zafra, Gonzalo Matilla-Cabello, José M Pinazo-Bandera, Raúl J Andrade, M Isabel Lucena, Marina Villanueva-Paz

{"title":"Modeling drug-induced liver injury: current status and future prospects.","authors":"Daniel E Di Zeo-Sánchez, Antonio Segovia-Zafra, Gonzalo Matilla-Cabello, José M Pinazo-Bandera, Raúl J Andrade, M Isabel Lucena, Marina Villanueva-Paz","doi":"10.1080/17425255.2022.2122810","DOIUrl":"https://doi.org/10.1080/17425255.2022.2122810","url":null,"abstract":"Introduction: Idiosyncratic drug-induced liver injury (iDILI) is a challenging and unpredictable multifactorial condition. At present, validated preclinical models for the prediction of the hepatotoxic potential of a given drug are scarce.Areas covered: This review intends to sum up the current knowledge about in vitro (including hepatocyte 2D cultures, cocultures with non-parenchymal cells, 3D configurations and non-typical closer to reality in vitro models), in vivo (covering models for immunological and oxidative stress features, humanized mouse-based and non-rodent models) and in silico approaches for iDILI modeling, highlighting the recent advances in each topic.Expert opinion: The future strategy for iDILI modeling should be patient-centered. Future animal and cell-based models, with more predictive value, will be easier to design by using a more translational approach based on mechanisms demonstrated in humans. Genetic and epigenetic information gathered from iDILI patients, together with data from in vitro and in vivo studies, could be used to develop sophisticated predictive in silico models to find compounds with iDILI potential. Collecting genetic, metabolic, and biomarker data from patient cohorts might be another option to create a 'fingerprint' characteristic of people at risk, allowing for the development of new, mechanistic strategies to enhance iDILI in vitro evaluation.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"555-573"},"PeriodicalIF":4.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40359552","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: 5

Respiratory aspiration during treatment with benzodiazepines, antiepileptic and antidepressant drugs in the pharmacovigilance database from VigiBase. VigiBase药物警戒数据库中苯二氮卓类药物、抗癫痫药物和抗抑郁药物治疗期间的呼吸误吸。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-09-01 Epub Date: 2022-09-13 DOI: 10.1080/17425255.2022.2122813

Carlos De Las Cuevas, Emilio J Sanz, Jose de Leon

{"title":"Respiratory aspiration during treatment with benzodiazepines, antiepileptic and antidepressant drugs in the pharmacovigilance database from VigiBase.","authors":"Carlos De Las Cuevas, Emilio J Sanz, Jose de Leon","doi":"10.1080/17425255.2022.2122813","DOIUrl":"https://doi.org/10.1080/17425255.2022.2122813","url":null,"abstract":"Introduction: Three psychotropic drug classes, benzodiazepines, antiepileptic drugs (AEDs) and antidepressants (ADs), whether used in treatment or overdose, may be associated with respiratory aspiration. Polypharmacy was defined by counting suspected drugs from these classes or two others, antipsychotics and opioids. The confounding effects of polypharmacy were considered in this study.Areas covered: VigiBase records of respiratory aspiration associated with benzodiazepines, AEDs, and/or ADs from inception until 5 September 2021, were reviewed. VigiBase, the World Health Organization's global pharmacovigilance database, uses a statistical signal for associations called the information component (IC).Expert opinion: The ICs (and IC025) were benzodiazepines 2.8 (and 2.6), AEDs 1.6 (and 1.5), and ADs 1.4 (and 1.3). The cases of respiratory aspiration associated with at least one drug from these 3 classes included: 1) 553 cases absent any known overdose (2.8 ± 1.7 drugs) and 2) 347 overdose cases (2.9 ± 1.8 drugs). Little support for the association of respiratory aspiration and benzodiazepine, AED or AD monotherapy in therapeutic dosages was found. Studies of the association between benzodiazepine monotherapy and respiration aspiration are needed in geriatric patients. ADs added to other medications increased lethality in all cases of respiratory aspiration including those associated with overdose, polypharmacy and/or major medical problems.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":"18 9","pages":"541-553"},"PeriodicalIF":4.3,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33448804","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: 1

A randomized, double-blind, single-dose, parallel phase I clinical trial to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar and bevacizumab in healthy Chinese subjects. 一项随机、双盲、单剂量、平行的I期临床试验，比较贝伐单抗生物仿制药和贝伐单抗在中国健康受试者中的生物等效性、免疫原性和安全性。

IF 4.3 3区医学

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-07-01 Epub Date: 2022-08-18 DOI: 10.1080/17425255.2022.2113382

Zhengzhi Liu, Zhenyue Gao, Wei Yang, Lixiu Zhang, Nan Xiao, Dongmei Qu, Zhengjie Su, Kaibo Xu, Guangwen Liu, Yanli Wang, Qing Ren, Shuang Yu, Yang Cheng, Yannan Zhou, Qiaohuan Deng, Yicheng Zhao, Zeyu Wang, Haimiao Yang

{"title":"A randomized, double-blind, single-dose, parallel phase I clinical trial to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar and bevacizumab in healthy Chinese subjects.","authors":"Zhengzhi Liu, Zhenyue Gao, Wei Yang, Lixiu Zhang, Nan Xiao, Dongmei Qu, Zhengjie Su, Kaibo Xu, Guangwen Liu, Yanli Wang, Qing Ren, Shuang Yu, Yang Cheng, Yannan Zhou, Qiaohuan Deng, Yicheng Zhao, Zeyu Wang, Haimiao Yang","doi":"10.1080/17425255.2022.2113382","DOIUrl":"https://doi.org/10.1080/17425255.2022.2113382","url":null,"abstract":"Background: Bevacizumab, a humanized monoclonal antibody against VEGF, can be used as a target therapy for colorectal cancer. A phase I clinical trial was conducted to compare the bioequivalence, immunogenicity, and safety of bevacizumab biosimilar (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Bevacizumab (Roche Diagnostics GmbH) in healthy Chinese males.Research design & method: Healthy Chinese subjects (N = 98) were randomly divided into two groups. A single-dose bevacizumab biosimilar or Bevacizumab was given per cycle. Plasma drug concentrations were detected by liquid chromatography-tandem mass spectrometry (LC-MC/MS) assay. We detected the levels of anti-drug antibody (ADA) to evaluate drug immunogenicity and the safety of drugs throughout the study.Results: The geometric mean ratios (GMRs) of AUC0-t, Cmax, and AUC0-∞ for bevacizumab biosimilar and Bevacizumab were 96.27%, 93.69%, and 97.01%, respectively. The 90% CIs were all within 80-125%, meeting the bioequivalence standards. The levels of ADA were similar. In addition, the two drugs both demonstrated excellent safety in the trial.Conclusion: This study showed that bevacizumab biosimilar and Bevacizumab had similar pharmacokinetics (PK) parameters and safety in healthy Chinese subjects.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"519-527"},"PeriodicalIF":4.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40607803","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