Xenobiotica最新文献_第7页

MicroRNA-Mediated Krüppel-Like Factor 4 Upregulation Induces Alternatively Activated Macrophage-Associated Marker and Chemokine Transcription in 4,4’-Methylene Diphenyl Diisocyanate Exposed Macrophages 微RNA介导的克鲁珀尔样因子4上调诱导暴露于4,4'-亚甲基二苯基二异氰酸酯的巨噬细胞中替代活化的巨噬细胞相关标记物和趋化因子的转录

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-04-03 DOI: 10.1080/00498254.2024.2334329

Chen-Chung Lin, Brandon F. Law, Justin M. Hettick

引用次数: 0

Pharmacokinetics and multi-peak phenomenon analysis of novel anti-Parkinson's drug FLZ after multi-dose in cynomolgus monkeys. 新型抗帕金森氏症药物 FLZ 在绒猴体内多次给药后的药代动力学和多峰现象分析

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-04-01 Epub Date: 2024-04-17 DOI: 10.1080/00498254.2024.2326475

Jiayu Li, Shuofeng Zhang, Rui Chen

{"title":"Pharmacokinetics and multi-peak phenomenon analysis of novel anti-Parkinson's drug FLZ after multi-dose in cynomolgus monkeys.","authors":"Jiayu Li, Shuofeng Zhang, Rui Chen","doi":"10.1080/00498254.2024.2326475","DOIUrl":"10.1080/00498254.2024.2326475","url":null,"abstract":"The novel anti-Parkinson disease drug, FLZ, had a complicated drug absorption and metabolise process reported in single-dose studies. A multi-peak absorption peak phenomenon was found.This study focused on the multi-dose pharmacokinetics (PK) characteristics of FLZ, T1, and T2 in cynomolgus monkeys and raised discussion on its multi-peak absorption situation. Different doses of FLZ ranging from 75 to 300 mg/kg were administered orally to 16 cynomolgus monkeys. The whole treatment period lasted for 42 days with FLZ once a day.The primary metabolites of FLZ were Target1 (T1) and Target2 (T2), which had plasma exposure (calculated as AUC0-24, day 42) approximately 2 and 10 times higher than the parent drug. The proportion of plasma exposure increase was lower than the proportion of dose increase in FLZ, T1, and T2.Gender influenced its exposure (AUC0-24) with approximately 3-fold higher in males than females. There was no significant accumulation of T1 and T2. Enterohepatic Circulation (EHC) and gastrointestinal (GI) tract absorption may be involved in the mechanism of multi-peak characteristics.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"201-210"},"PeriodicalIF":1.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337014","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

Exploring the pharmacokinetics of second-generation cephalosporin, cefaclor: a systematic review in healthy and diseased populations. 探索第二代头孢菌素头孢克洛的药代动力学：对健康人群和患病人群的系统综述

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-04-01 Epub Date: 2024-04-02 DOI: 10.1080/00498254.2024.2333009

Tahir Saleem, Ammara Zamir, Muhammad Fawad Rasool, Imran Imran, Hamid Saeed, Faleh Alqahtani

{"title":"Exploring the pharmacokinetics of second-generation cephalosporin, cefaclor: a systematic review in healthy and diseased populations.","authors":"Tahir Saleem, Ammara Zamir, Muhammad Fawad Rasool, Imran Imran, Hamid Saeed, Faleh Alqahtani","doi":"10.1080/00498254.2024.2333009","DOIUrl":"10.1080/00498254.2024.2333009","url":null,"abstract":"Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans.Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor.Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC0-t) and maximum plasma concentration (Cmax) increase in a dose-dependent manner. The AUC0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a Cmax 2.2 times higher than that of normal subjects. A significant increase in Cmax was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens.This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"171-181"},"PeriodicalIF":1.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190187","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

Reversible oxidation/reduction steps in the metabolic degradation of the glycerol side chain of the S1P₁ modulator ponesimod. S1P1 调节剂 ponesimod 的甘油侧链代谢降解过程中的可逆氧化/还原步骤。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-04-01 Epub Date: 2024-03-01 DOI: 10.1080/00498254.2024.2319812

Alexander Treiber, Swen Seeland, Jérôme Segrestaa, Cyrille Lescop, Martin H Bolli

{"title":"Reversible oxidation/reduction steps in the metabolic degradation of the glycerol side chain of the S1P1 modulator ponesimod.","authors":"Alexander Treiber, Swen Seeland, Jérôme Segrestaa, Cyrille Lescop, Martin H Bolli","doi":"10.1080/00498254.2024.2319812","DOIUrl":"10.1080/00498254.2024.2319812","url":null,"abstract":"1. Ponesimod is a selective modulator of the sphingosine 1-phosphate receptor 1 (S1P1) approved for the treatment of active relapsing forms of multiple sclerosis. The chemical structure of ponesimod contains a glycerol side chain which is the major target of drug metabolism in humans.2. The two major metabolic pathways give the acids M12 (-OCH2CH(OH)COOH) and M13 (-OCH2COOH). While the former results from oxidation of the terminal alcohol, the mechanism yielding the chain-shortened acid M13 is less obvious. A detailed mechanistic study with human liver microsomes and hepatocytes using ponesimod, M12 and some of the suspected intermediates revealed an unexpectedly complex pattern of enzyme-mediated and chemical reactions.3. Metabolic pathways for both acids were not independent and several of the transformations were reversible, depending on reaction conditions. Formation of M13 occurred either via initial oxidation of the secondary alcohol, or as a downstream process starting from M12.4. The phenol metabolite M32 was produced as part of several pathways. Control experiments at various pH values and in the absence of metabolising enzymes support the conclusion that its formation resulted from chemical degradation rather than from metabolic processes.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"182-194"},"PeriodicalIF":1.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944521","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

Thank you to reviewers 感谢审稿人

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-18 DOI: 10.1080/00498254.2024.2303194

引用次数: 0

Preclinical pharmacokinetic investigation of the bioavailability and skin distribution of HY-072808 ointment, a novel drug candidate for the treatment of atopic dermatitis, in minipigs by a newly LC-MS/MS method. 采用新的 LC-MS/MS 方法对治疗特应性皮炎的新型候选药物 HY-072808 软膏在小型猪体内的生物利用度和皮肤分布进行临床前药代动力学研究。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-01 Epub Date: 2024-04-02 DOI: 10.1080/00498254.2024.2333007

Li Shao, Jiajia Mo, Qinlong Xu, Guangwei He, Chunyu Xing, Zhaoxing Chu

{"title":"Preclinical pharmacokinetic investigation of the bioavailability and skin distribution of HY-072808 ointment, a novel drug candidate for the treatment of atopic dermatitis, in minipigs by a newly LC-MS/MS method.","authors":"Li Shao, Jiajia Mo, Qinlong Xu, Guangwei He, Chunyu Xing, Zhaoxing Chu","doi":"10.1080/00498254.2024.2333007","DOIUrl":"10.1080/00498254.2024.2333007","url":null,"abstract":"HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC-MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1-7.6% after transdermal application of 1-4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"138-149"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159142","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

Effects of pharmacogenetics on pharmacokinetics and toxicity of doxorubicin in Egyptian breast cancer patients. 药物遗传学对埃及乳腺癌患者多柔比星药代动力学和毒性的影响

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-01 Epub Date: 2024-04-02 DOI: 10.1080/00498254.2024.2330493

N F Ebaid, K S Abdelkawy, M A Shehata, H F Salem, G Magdy, R R S Hussein, F Elbarbry

{"title":"Effects of pharmacogenetics on pharmacokinetics and toxicity of doxorubicin in Egyptian breast cancer patients.","authors":"N F Ebaid, K S Abdelkawy, M A Shehata, H F Salem, G Magdy, R R S Hussein, F Elbarbry","doi":"10.1080/00498254.2024.2330493","DOIUrl":"10.1080/00498254.2024.2330493","url":null,"abstract":"This study investigates the impact of single nucleotide polymorphisms in genes (SLC22A16 and CBR1) involved in the pharmacokinetics and toxicity of doxorubicin (DOX) in Egyptian female patients with breast cancer.Patients administered DOX (60 mg/m2) for 4 cycles every 3 weeks. The peak DOX plasma concentration was measured using a validated chromatographic method. The genotyping for the selected SNPs, SLC22A16 T > C (rs714368), and CBR1 C > T (rs20572), was performed by RT-PCR. Patients were monitored for hematological and cardiac toxicities.The variant carriers of CBR1 C > T (rs20572) exhibited significantly higher DOX concentration, but no significant association to DOX-induced hematological toxicity. On the other hand, SLC22A16 T > C (rs714368) had no significant influence on DOX plasma concentration, but was significantly correlated with lower risk of neutropenia (OR 0.31, 95% CI 0.12-0.75, p = 0.01) and leukopoenia (OR 0.18, 95% CI 0.07-0.5, p = 0.001). DOX-related cardiotoxicity was correlated with the cumulative dose of DOX (R = 0.238, p = 0.017), but not with any of the two examined SNPs.Genetic polymorphisms in SLC22A16 and CBR1 may explain the inter-individual variations in DOX pharmacokinetics and toxicity. Using pharmacogenetic testing is important to customise drug therapy for cancer patients treated with anthracyclines.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"160-170"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140835","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

Development of a physiologically based pharmacokinetic model for levetiracetam in patients with renal impairment to guide dose adjustment based on steady-state peak/trough concentrations. 针对肾功能受损患者开发基于生理的左乙拉西坦药代动力学模型，以便根据稳态峰/槽浓度指导剂量调整。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-01 Epub Date: 2024-02-21 DOI: 10.1080/00498254.2024.2317888

Rongrong Wang, Tianlin Wang, Xueliang Han, Mengli Chen, Shu Li

{"title":"Development of a physiologically based pharmacokinetic model for levetiracetam in patients with renal impairment to guide dose adjustment based on steady-state peak/trough concentrations.","authors":"Rongrong Wang, Tianlin Wang, Xueliang Han, Mengli Chen, Shu Li","doi":"10.1080/00498254.2024.2317888","DOIUrl":"10.1080/00498254.2024.2317888","url":null,"abstract":"Levetiracetam may cause acute renal failure and myoclonic encephalopathy at high plasma levels, particularly in patients with renal impairment. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict levetiracetam pharmacokinetics in Chinese adults with epilepsy and renal impairment and define appropriate levetiracetam dosing regimen.PBPK models for healthy subjects and epilepsy patients with renal impairment were developed, validated, and adapted. Furthermore, we predicted the steady-state trough and peak concentrations of levetiracetam in patients with renal impairment using the final PBPK model, thereby recommending appropriate levetiracetam dosing regimens for different renal function stages. The predicted maximum plasma concentration (Cmax), time to maximum concentration (Tmax), area under the plasma concentration-time curve (AUC) were in agreement (0.8 ≤ fold error ≤ 1.2) with the observed, and the fold error of the trough concentrations in end-stage renal disease (ESRD) was 0.77 - 1.22. The prediction simulations indicated that the recommended doses of 1000, 750, 500, and 500 mg twice daily for epilepsy patients with mild, moderate, severe renal impairment, and ESRD, respectively, were sufficient to achieve the target plasma concentration of levetiracetam.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"116-123"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724209","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

Prediction of combination effect of quinidine on the pharmacokinetics of tipepidine using a physiologically based pharmacokinetic model. 利用基于生理学的药代动力学模型预测奎尼丁对替普匹定药代动力学的联合影响。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-01 Epub Date: 2024-01-17 DOI: 10.1080/00498254.2024.2304129

Shun Hayashi, Hiroko Kawaguchi, Takao Watanabe, Izuru Miyawaki, Tatsuki Fukami, Miki Nakajima

{"title":"Prediction of combination effect of quinidine on the pharmacokinetics of tipepidine using a physiologically based pharmacokinetic model.","authors":"Shun Hayashi, Hiroko Kawaguchi, Takao Watanabe, Izuru Miyawaki, Tatsuki Fukami, Miki Nakajima","doi":"10.1080/00498254.2024.2304129","DOIUrl":"10.1080/00498254.2024.2304129","url":null,"abstract":"Tipepidine, an antitussive drug, has been reported to have central pharmacological effects and can be expected to be safely repositioned as treatment for psychiatric disorders. Since tipepidine requires three doses per day, development of a once-daily medication would be highly beneficial. Previously, we reported that combination use with quinidine, a CYP2D6 inhibitor, prolongs the half-life of tipepidine in chimeric mice with humanised liver.In this study, to predict this combination effect in humans, a physiologically based pharmacokinetic (PBPK) model was developed, and quantitative simulation was conducted. The simulation results indicated that concomitant administration of tipepidine with quinidine increased the predicted Cmax, AUC, and t1/2 of tipepidine in the Japanese population by 3.4-, 6.6-, and 2.4-fold, respectively.Furthermore, to compare with another approach that aims to prolong the half-life, the PK profile of tipepidine administered in hypothetical extended-release form was simulated. Extended-release form was predicted to be more influenced by CYP2D6 genotype than combination with quinidine, and the predicted plasma exposure was markedly increased in poor metabolizers, potentially leading to adverse effects.In conclusion, quantitative simulation using the PBPK model suggests the feasibility of the safe repositioning of tipepidine as a once-daily medication in combination with quinidine.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"107-115"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139404603","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

Sodium dodecylbenzene sulphonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish. 洗涤剂中的十二烷基苯磺酸钠（SDBS）：对 D. rerio 鱼鳃、皮肤和血液的作用。

IF 1.8 4区医学

Xenobiotica Pub Date : 2024-03-01 Epub Date: 2024-02-16 DOI: 10.1080/00498254.2024.2316646

Eduardo Libanio Reis Santos, Odaiza Silva, Jeffesson de Oliveira-Lima, Maria Izabel Camargo-Mathias

{"title":"Sodium dodecylbenzene sulphonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish.","authors":"Eduardo Libanio Reis Santos, Odaiza Silva, Jeffesson de Oliveira-Lima, Maria Izabel Camargo-Mathias","doi":"10.1080/00498254.2024.2316646","DOIUrl":"10.1080/00498254.2024.2316646","url":null,"abstract":"1. Sodium dodecylbenzene sulphonate (SDBS) is one of the surfactants used worldwide in detergents which, due to high residual discharges, has great potential to cause ecotoxicological impacts. Therefore, the sublethal effects of SDBS on the gills and skin of male Danio rerio fish were investigated.2. The fish were distributed into three groups: GC (control), GT1 (0.25 mg/L of SDBS), and GT2 (0.5 mg/L of SDBS) and exposed for 21 days. After the experiment, histopathological analyses of the gills, histochemical analyses (counting of mucous cells), and biochemical analyses (antioxidant defense enzyme analysis, SOD, and CAT) were conducted.3. A significant increase (p < 0.05) in the incidence of circulatory disorders, progressive, and regressive alterations occurred in the GT1 and GT2 groups. Due to these changes, the total histopathological index of the gills was higher in these groups. Mucous cells in the gills and skin increased. There was an increase in SOD activity and a reduction in CAT activity in these groups. Haematology revealed neutrophilia and lymphocytosis in the blood of GT1 and GT2.4. The results clearly demonstrate that a 21-day exposure to SDBS causes severe morphophysiological damage to the gills, skin, and blood of D. rerio fish.","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"150-159"},"PeriodicalIF":1.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708014","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