Regulatory Toxicology and Pharmacology最新文献_第5页

Safety assessment of drug impurities for patient safety: A comprehensive review 针对患者安全的药物杂质安全评估：全面综述。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-05 DOI: 10.1016/j.yrtph.2024.105715

Frank Liu

{"title":"Safety assessment of drug impurities for patient safety: A comprehensive review","authors":"Frank Liu","doi":"10.1016/j.yrtph.2024.105715","DOIUrl":"10.1016/j.yrtph.2024.105715","url":null,"abstract":"<div><div>Drug impurities are undesirable but unavoidable chemicals which can occur throughout the drug life cycle. The safety implications of drug impurities can be significant given that they can impact safety, quality, and efficacy of drug products and that certain drug impurities are mutagenic, carcinogenic, or teratogenic. The characteristics of drug impurities could be specific to drug modalities (e.g., small molecules vs. biologics). The commonly encountered drug impurities include elemental impurity, residual solvent, organic impurity, host cell protein and DNA, residual viral vector, extractable and leachable, and particle. They can cause various adverse effects such as immunogenicity, infection, genotoxicity, and carcinogenicity upon significant exposure. Therefore, the effective control of these drug impurities is central for patient safety. Regulations and guidelines are available for drug developers to manage them. Their qualification is obtained based on authoritative qualification thresholds or safety assessment following the classic toxicological risk assessment. The current review focuses on the safety assessment science and methodology used for diverse types of drug impurities. Due to the different nature of diverse drug impurities, their safety assessment represents a significant challenge for drug developers.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105715"},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative risk assessments of skin sensitization for 26 allergens in different consumer products in the Saudi market 对沙特市场不同消费品中的 26 种过敏原进行皮肤过敏定量风险评估。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-03 DOI: 10.1016/j.yrtph.2024.105714

Adnan S. AL-Mussallam , Rawan S. Alshathri , Bart Desmedt , Fahad S. Aldawsari , Eric Deconinck , Omniyah A. Alharthi , Abdullah T. Bawazir

{"title":"Quantitative risk assessments of skin sensitization for 26 allergens in different consumer products in the Saudi market","authors":"Adnan S. AL-Mussallam , Rawan S. Alshathri , Bart Desmedt , Fahad S. Aldawsari , Eric Deconinck , Omniyah A. Alharthi , Abdullah T. Bawazir","doi":"10.1016/j.yrtph.2024.105714","DOIUrl":"10.1016/j.yrtph.2024.105714","url":null,"abstract":"<div><div>Fragrance chemicals are ubiquitous in cosmetics; however, they have been linked to allergic contact dermatitis. Allergy prevention involves two main strategies. Firstly, consumers are protected by limiting the maximum concentration of fragrance in a given product to avoid inducing allergies. Secondly, consumers who are already sensitized are protected by having the presence of such fragrance communicated to them. In this study, a validated GC-MS method was employed to quantify 26 allergens in 108 products marketed in Saudi Arabia.Additionally, a quantitative risk assessment (QRA) was performed on the studied cosmetics to determine the risk of inducing allergies. The results indicated that most allergens were present at acceptable concentrations, while 19 products carried a risk of inducing allergies. Furthermore, Lilial and Lyral, two prohibited fragrances, were detected in 97 products. It should be emphasized that this is the first study conducted in Saudi Arabia to evaluate the safety of the well-known 26 fragrance allergens. Hence, this study can potentially serve as a regional standard for future research.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105714"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support 绘制新型精神活性物质地图：利用 GIS 技术进行先进的全球监控和政策支持。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-10-02 DOI: 10.1016/j.yrtph.2024.105713

Ting-Jung Ku , Tien-Chueh Kuo , Olivia A. Lin , Yufeng Jane Tseng

{"title":"Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support","authors":"Ting-Jung Ku , Tien-Chueh Kuo , Olivia A. Lin , Yufeng Jane Tseng","doi":"10.1016/j.yrtph.2024.105713","DOIUrl":"10.1016/j.yrtph.2024.105713","url":null,"abstract":"<div><div>The escalating challenge of New Psychoactive Substances (NPS) necessitates enhanced global monitoring and analysis capabilities. This study introduces an advanced interactive visualization tool that employs Geographic Information System (GIS) technologies to improve the functionality of the UNODC's Early Warning Advisory. The tool enables dynamic observation and analysis of NPS's geographical and temporal distribution, thereby facilitating a comprehensive understanding of their public health impacts. By incorporating detailed choropleth maps and annual and cumulative bar charts, the tool allows policymakers and researchers to visually track and analyze trends in NPS usage and control efforts across different regions. The results demonstrate the tool's effectiveness in providing actionable insights, which support the strategic development of public health policies and interventions to curb the global rise in NPS usage. This initiative illustrates the essential role of digital tools in enhancing public health strategies and responses to emerging drug trends. This rising challenge underscores the urgent need for innovative solutions in monitoring drug trends, a theme explored in this paper. The web tool is available at <span><span>https://nps-vis.cmdm.tw</span><svg><path></path></svg></span>, and the code is available at <span><span>https://github.com/CMDM-Lab/nps-vis</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105713"},"PeriodicalIF":3.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimizing the detection of N-nitrosamine mutagenicity in the Ames test 优化艾姆斯试验中 N-亚硝胺致突变性的检测。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-28 DOI: 10.1016/j.yrtph.2024.105709

Robert H. Heflich , Michelle E. Bishop , Roberta A. Mittelstaedt , Jian Yan , Sharon K. Guerrero , Audrey M. Sims , Kamela Mitchell , Nyosha Moore , Xilin Li , Nan Mei , Rosalie K. Elespuru , Sruthi T. King , David A. Keire , Naomi L. Kruhlak , Robert T. Dorsam , Andre S. Raw , Karen L. Davis Bruno , Timothy J. McGovern , Aisar H. Atrakchi

{"title":"Optimizing the detection of N-nitrosamine mutagenicity in the Ames test","authors":"Robert H. Heflich , Michelle E. Bishop , Roberta A. Mittelstaedt , Jian Yan , Sharon K. Guerrero , Audrey M. Sims , Kamela Mitchell , Nyosha Moore , Xilin Li , Nan Mei , Rosalie K. Elespuru , Sruthi T. King , David A. Keire , Naomi L. Kruhlak , Robert T. Dorsam , Andre S. Raw , Karen L. Davis Bruno , Timothy J. McGovern , Aisar H. Atrakchi","doi":"10.1016/j.yrtph.2024.105709","DOIUrl":"10.1016/j.yrtph.2024.105709","url":null,"abstract":"<div><div>Accurately determining the mutagenicity of small-molecule <em>N</em>-nitrosamine drug impurities and nitrosamine drug substance-related impurities (NDSRIs) is critical to identifying mutagenic and cancer hazards. In the current study we have evaluated several approaches for enhancing assay sensitivity for evaluating the mutagenicity of <em>N</em>-nitrosamines in the bacterial reverse mutagenicity (Ames) test. Preincubation assays were conducted using five activation conditions: no exogenous metabolic activation and metabolic activation mixes employing both 10% and 30% liver S9 from hamsters and rats pretreated with inducers of enzymatic activity. In addition, preincubations were conducted for both 60 min and 30 min. These test variables were evaluated by testing 12 small-molecule <em>N</em>-nitrosamines and 17 NDSRIs for mutagenicity in <em>Salmonella typhimurium</em> tester strains TA98, TA100, TA1535, and TA1537, and <em>Escherichia coli</em> strain WP2 uvrA (pKM101). Eighteen of the 29 <em>N</em>-nitrosamine test substances tested positive under one or more of the testing conditions and all 18 positives could be detected by using tester strains TA1535 and WP2 uvrA (pKM101), preincubations of 30 min, and S9 mixes containing 30% hamster liver S9. In general, the conditions under which NDSRIs were mutagenic were similar to those found for small-molecule <em>N</em>-nitrosamines.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105709"},"PeriodicalIF":3.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rethinking the necessity of long-term toxicity studies for biotherapeutics using weight of evidence assessment 利用证据权重评估重新思考生物治疗药物长期毒性研究的必要性。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-26 DOI: 10.1016/j.yrtph.2024.105710

Payal Rana , Brett Hollingshead , Raja Mangipudy

{"title":"Rethinking the necessity of long-term toxicity studies for biotherapeutics using weight of evidence assessment","authors":"Payal Rana , Brett Hollingshead , Raja Mangipudy","doi":"10.1016/j.yrtph.2024.105710","DOIUrl":"10.1016/j.yrtph.2024.105710","url":null,"abstract":"<div><div>The registration of biotherapeutics for chronic indications requires 6-month toxicity studies. However, extensive experience has shown that the non-clinical safety profiles of biotherapeutics are generally predictable. This suggests that conducting multiple studies, especially a 6-month study may not be necessary. In a meta-analysis of biologics developed for non-oncology indications over last 25 years at Pfizer, we compared organ system findings between short-term (1–3 month) and long-term (6-month) animal studies. Our goal was to determine if there were differences in the safety profiles between the two study durations and their relevance to human risk assessment. Our analysis revealed that most clinically relevant toxicities could be detected in shorter-term studies (87%; 26/30 programs). This suggests either an undifferentiated safety profile between short-and long-term studies, or anticipated toxicities based on the modality, such as immunogenicity or exaggerated pharmacology. However, for 4 out of 30 programs (13%), long-term studies did identify either potential new toxicities or more severe manifestation of exaggerated pharmacology, leading to modifications in clinical trial designs and human risk assessment. Our experience suggests that 3-month toxicity studies may be sufficient to support late-stage clinical development for a majority of standard biotherapeutic programs. This pragmatic and science-based approach aligns with the goal of advancing 3R's initiatives in nonclinical safety assessment.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105710"},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide 重新评估四甲基氢氧化铵 28 天口服重复剂量毒性研究中雄性大鼠心脏重量减少的情况。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-26 DOI: 10.1016/j.yrtph.2024.105712

Akira Kawashima, Kaoru Inoue

{"title":"Re-evaluation of the reduced heart weights in male rats in a 28-day oral repeated-dose toxicity study of tetramethylammonium hydroxide","authors":"Akira Kawashima, Kaoru Inoue","doi":"10.1016/j.yrtph.2024.105712","DOIUrl":"10.1016/j.yrtph.2024.105712","url":null,"abstract":"<div><div>We recently conducted a detailed hazard assessment of tetramethylammonium hydroxide (TMAH), a priority chemical substance under the Japan Chemical Substances Control Law. During this assessment, there was debate regarding the reduced heart weight observed in the treated male groups in the 28-day rat oral repeated-dose toxicity study. This finding was not observed in females in this study and in both sexes of oral toxicity studies for tetramethylammonium chloride (TMAC) or tetramethylammonium hydrogen phthalate (TMAHP). Unpublished individual data from the oral TMAH developmental and reproductive toxicity (DART) screening study were also obtained; no effect on heart weight was observed. In addition, background data on rat heart weight from six 28-day oral toxicity studies conducted in the same facility, year, strain, age, and breeder as the TMAH study were obtained from the Japan Existing Chemical Substances Database (JECDB). These investigations suggest that the statistically significant lower heart weight in the treated males in the 28-day toxicity study is likely caused by an incidental skewing of individuals with heavier heart weights toward control male groups and is not due to TMAH treatment. Thus, it is worthwhile to include as much relevant data as possible to confirm or refute unexpected findings in toxicity studies.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105712"},"PeriodicalIF":3.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 0

N-Nitrosamine drug substance related impurities (NDSRIs) – A proposal for the addition of subcategories to carcinogenic potency categorization approach categories 1 and 2 for NDSRIs with a molecular weight > 200 Da N-亚硝胺药物物质相关杂质（NDSRIs）--关于在致癌性分类方法类别 1 和 2 中增加分子量大于 200 Da 的 NDSRIs 子类别的建议。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-24 DOI: 10.1016/j.yrtph.2024.105704

Joel Bercu , Olivier Dirat , Krista Dobo , Robert Jolly , Michelle Kenyon , James Harvey , Raphael Nudelman , Graham Smith , Alejandra Trejo-Martin , Michael Urquhart

{"title":"N-Nitrosamine drug substance related impurities (NDSRIs) – A proposal for the addition of subcategories to carcinogenic potency categorization approach categories 1 and 2 for NDSRIs with a molecular weight > 200 Da","authors":"Joel Bercu , Olivier Dirat , Krista Dobo , Robert Jolly , Michelle Kenyon , James Harvey , Raphael Nudelman , Graham Smith , Alejandra Trejo-Martin , Michael Urquhart","doi":"10.1016/j.yrtph.2024.105704","DOIUrl":"10.1016/j.yrtph.2024.105704","url":null,"abstract":"<div><div>The carcinogenicity potency categorization approach (CPCA) derived and harmonized by Health Authorities was a significant milestone, as it defined molecular properties that allowed for the rapid evaluation of the chemical structures of N-nitrosamine drug substance related impurities (NDSRIs) and the assignment of associated lifetime Acceptable Intake (AI) limits to inform on appropriate impurity control strategies in certain drug products. Nonetheless, it is important to continue to refine and improve on the CPCA based upon data-derived evidence. Herein, we focus on the default CPCA AI for NDSRIs, which is largely based on the small molecule N-nitrosamines (NAs). Considering the carcinogenic potency of NAs with a molecular weight >200 Da (NDSRIs molecular weight is typically 200–600 Da), we propose that in the absence of any compound specific data, the lowest lifetime Acceptable Intake for NAs, such as NDSRIs, should be 10x less (i.e., 150 ng/day) than the ICH M7 Threshold of Toxicological Concern of 1500 ng/day, (even for NDSRIs that are considered CPCA Category 1 and 2) which would conservatively result in a theoretical cancer risk of <1 in 100,000.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"154 ","pages":"Article 105704"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The new paradigm in animal testing – “3Rs alternatives” 动物试验的新典范--"3Rs 替代品"。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-20 DOI: 10.1016/j.yrtph.2024.105705

Wen Tsin Poh, Johnson Stanslas

{"title":"The new paradigm in animal testing – “3Rs alternatives”","authors":"Wen Tsin Poh, Johnson Stanslas","doi":"10.1016/j.yrtph.2024.105705","DOIUrl":"10.1016/j.yrtph.2024.105705","url":null,"abstract":"<div><div>Regulatory studies have revolutionised over time. Today, the focus has shifted from animal toxicity testing to non-animal for regulatory safety testing. This move is in line with the international 3Rs (Replacement, Reduction, and Refinement) principle and has also changed the regulator's perspective. The 3R principle has stimulated changes in policy, regulations, and new approaches to safety assessment in drug development in many countries. The 3Rs approach has led to the discovery and application of new technologies and more human-relevant <em>in vitro</em> approaches that minimise the use of animals including non-human primates, in research and improve animal welfare. In 2016, the European Medicines Agency published the Guidelines on the principles of regulatory acceptance of 3Rs testing approaches, followed by a conceptual paper in 2023 to align with current 3R standards. Additionally, the United States Food and Drug Administration passed new legislation in 2023 that no longer requires all new human drugs to be tested on animals, which will change the current testing paradigm. This review paper provides the adoption of the 3Rs and the current regulatory perspective regarding their implementation.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105705"},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Botanical-induced toxicity: Liver injury and botanical-drug interactions. A report on a society of Toxicology Annual Meeting symposium 植物药引起的毒性：肝损伤和植物药与药物的相互作用毒理学会年会专题讨论会报告。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-19 DOI: 10.1016/j.yrtph.2024.105708

Igor Koturbash , R. Philip Yeager , Constance A. Mitchell , Stephen Ferguson , Victor J. Navarro , Mary F. Paine , Amy L. Roe

{"title":"Botanical-induced toxicity: Liver injury and botanical-drug interactions. A report on a society of Toxicology Annual Meeting symposium","authors":"Igor Koturbash , R. Philip Yeager , Constance A. Mitchell , Stephen Ferguson , Victor J. Navarro , Mary F. Paine , Amy L. Roe","doi":"10.1016/j.yrtph.2024.105708","DOIUrl":"10.1016/j.yrtph.2024.105708","url":null,"abstract":"<div><div>Botanical supplements and herbal products are widely used by consumers for various purported health benefits, and their popularity is increasing. Some of these natural products can have adverse effects on liver function and/or interact with prescription and over-the-counter (OTC) medications. Ensuring the safety of these readily available products is a crucial public health concern; however, not all regulatory authorities require premarket safety review and/or testing. To address and discuss these and other emerging needs related to botanical safety, a symposium was held at the Society of Toxicology Annual Meeting in Salt Lake City (UT) on March 11, 2024. The symposium addressed the latest research on botanical-induced liver toxicity and botanical-drug interactions, including new approach methods to screen for toxicity, challenges in assessing the safety of botanicals, and relating human adverse events to specific products. The presentations and robust panel discussion between the speakers and audience highlighted the need for further research and collaboration to improve the safety of botanical supplements and herbal products, with the ultimate goal of protecting consumer health. Although utility of many of the modern tools presented in the symposium requires further study, the synergistic efforts of diverse experts hold promise for effective prediction and evaluation of botanical-induced hepatotoxicity and botanical-drug interaction potential.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105708"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0273230024001491/pdfft?md5=b5bac393db266260b93676b9c48f5214&pid=1-s2.0-S0273230024001491-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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: 0

Residue depletion profiles and withdrawal intervals of florfenicol and its metabolite florfenicol amine in plasma and milk of lactating goats after repeated subcutaneous administrations 重复皮下注射后哺乳山羊血浆和乳汁中氟苯尼考及其代谢物氟苯尼考胺的残留消耗曲线和停药间隔时间。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-09-18 DOI: 10.1016/j.yrtph.2024.105707

Qiran Chen , Zhoumeng Lin , Jennifer L. Davis , Emily Toney , Maaike O. Clapham , Xue Wu , Lisa A. Tell

{"title":"Residue depletion profiles and withdrawal intervals of florfenicol and its metabolite florfenicol amine in plasma and milk of lactating goats after repeated subcutaneous administrations","authors":"Qiran Chen , Zhoumeng Lin , Jennifer L. Davis , Emily Toney , Maaike O. Clapham , Xue Wu , Lisa A. Tell","doi":"10.1016/j.yrtph.2024.105707","DOIUrl":"10.1016/j.yrtph.2024.105707","url":null,"abstract":"<div><div>Florfenicol is a broad-spectrum and bacteriostatic antibiotic with a time-dependent killing action. It is commonly used to treat respiratory diseases in goats in an extra-label manner. This study aimed to determine the plasma pharmacokinetics and milk residue depletion profiles and calculate the milk withdrawal interval (WDI) of florfenicol and its main metabolite florfenicol amine in lactating goats. Five healthy lactating goats were administered with 40 mg/kg florfenicol by subcutaneous injection, twice, 96 h apart. Plasma and milk samples were collected up to 864 h post the first injection. Non-compartmental analysis was used to estimate the plasma pharmacokinetic parameters. Milk WDIs were calculated using the U.S. Food and Drug Administration (FDA) method and European Medicines Agency (EMA) method. A Monte Carlo simulation was performed to generate simulated data for five virtual animals to meet the data requirement of the FDA method. The calculated milk WDIs based on florfenicol, florfenicol amine, and the combined (the sum of florfenicol and florfenicol amine) were 720.28, 690.45, and 872.69 h after the last injection using the FDA method. In conclusion, this study improves our understanding on the plasma pharmacokinetics and milk residue depletion kinetics of florfenicol and florfenicol amine in lactating ruminants after subcutaneous injections.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"153 ","pages":"Article 105707"},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0