Devran Coskun, Orhan Corum, Duygu Durna Corum, Kamil Uney
{"title":"Comparative Pharmacokinetics of İntravenous Enrofloxacin in One- Six- And Twelve-Month-Old Sheep","authors":"Devran Coskun, Orhan Corum, Duygu Durna Corum, Kamil Uney","doi":"10.2174/0113892002278220231208072351","DOIUrl":"https://doi.org/10.2174/0113892002278220231208072351","url":null,"abstract":"Background: Enrofloxacin (ENR) is a fluoroquinolone antibiotic approved for use in sheep of all ages. The body composition and metabolic capability change with age. These changes may alter the pharmacokinetics of drugs and thus their effect. Therefore, the pharmacokinetics of drugs need to be established in target-age animals Objective: To determine the pharmacokinetics of ENR and its active metabolite, ciprofloxacin (CIP), following a single intravenous administration of ENR at a dose of 10 mg/kg in different ages of sheep. Methods: The study was carried out in the one-, six- and twelve-month age period of the sheep. A single dose of 10 mg/kg ENR was administered intravenously through the jugular vein to sheep in all age periods. ENR and CIP plasma concentrations were determined using HPLC–UV and analyzed using a non-compartmental method. Results: ENR was detected in the plasma until 36 h in one-month-old and up to 24 h in other ages. CIP was detected in the plasma up to 24 h in all age groups. The t1/2ʎz and Vdss were significantly higher in one-month-old sheep than in six and twelve-months old sheep. There was no difference in ClT and AUC values in different age groups. AUC0-∞CIP/AUC0-∞ENR ratios were higher in one-month-old than in six- and twelve-months sheep. Conclusion: The most important pharmacokinetic changes associated with aging in sheep are decreased Vdss and t1/2ʎz of ENR and the low ratio metabolizing of ENR to CIP. Pharmacokinetic/pharmacodynamic data showed that ENR after IV administration of 10 mg/kg dose provided the optimal AUC0–24/MIC90 ratios for E. coli, P. multocida and Mycoplasma spp. (>125) with MIC of 0.37 µg/mL and for S. aureus (>30) with MIC of 0.5 µg/mL in all ages of sheep.","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"60 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139028919","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}
Mohammad Hossein Asgarshamsi, Mehrdad Mohammadpour Dehkordi, Seyed Mohamad Reza Nazifi, Krzysztof K. Zborowski
{"title":"Theoretical Evaluation of Oleocanthal Reactive Centers","authors":"Mohammad Hossein Asgarshamsi, Mehrdad Mohammadpour Dehkordi, Seyed Mohamad Reza Nazifi, Krzysztof K. Zborowski","doi":"10.2174/0113892002276499231201094142","DOIUrl":"https://doi.org/10.2174/0113892002276499231201094142","url":null,"abstract":"Background:: Decarboxymethyl ligstroside aglycone (oleocanthal) is an essential component of olive oil. It is therefore interesting to study its metabolism in the human body. In order to find the best possible starting point for this metabolism, a theoretical study was carried out using DFT calculations and docking studies. Methods:: The DFT, B3LYP/6-311++G** and the PCM solvation model calculations were used to study the initial process of oleocanthal metabolism by the CYP1A2 enzyme. Structures of radicals formed by homolytic dissociation of hydrogen atoms from the oleocanthal structure were obtained and their properties were studied. Several parameters such as HOMO and LUMO energy gaps, Bond Dissociation Energy (BDE), hardness, and spin density of possible oleocanthal radicals were taken into account. Docking of oleocanthal into an enzyme binding pocket was also performed to locate the most probably metabolic site. Detailed analysis of the theoretical results allows the determination of the most likely reaction sites in oleocanthal. The mode of binding of oleocanthal to the CYP1A2 enzyme was also predicted. Results:: The results of the molecular docking studies are in agreement with the calculated quantum parameters. The theoretical predictions were compared with experimental data available in the scientific literature. A high correlation between theoretical calculations and experimental data was observed. The most likely site of oleocanthal metabolism was identified. Conclusion:: The results of our research support the usefulness of theoretical calculations in predicting metabolic pathways.","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"152 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692643","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}
{"title":"Pharmacokinetics, Mass Balance, Tissue Distribution and Metabolism of [14C]101BHG-D01, a Novel Muscarinic Receptor Antagonist, in Rats","authors":"Huaye Gao, Cheng Yang, Wenhui Hu, Juefang Ding, Xingxing Diao, Yuandong Zheng, Chang Shu, Li Ding","doi":"10.2174/0113892002275839231205111422","DOIUrl":"https://doi.org/10.2174/0113892002275839231205111422","url":null,"abstract":"Background:: 101BHG-D01, a novel long-acting and selective muscarinic receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD), is undergoing Phase Ib clinical trial in patients and has shown its potential efficacy. Its preparation method and medical use thereof have been patented in the United States (Patent No.US9751875B2). Objective:: In this study, the pharmacokinetics, mass balance, tissue distribution and metabolism of radioactive 101BHG-D01 were investigated in rats after an intravenous dose of 1 mg/kg [14C]101BHG-D01 (100 μCi/kg). objective: In this study, the pharmacokinetics, mass balance, tissue distribution and metabolism of radioactive 101BHG-D01 were investigated in rats after an intravenous dose of 1 mg/kg [14C]101BHG-D01 (100 µCi/kg). Methods:: Radioactivity in rat plasma, urine, feces, and tissues was measured by liquid scintillation counting (LSC), and metabolite profiling and identification were conducted by UHPLC-β-RAM and UHPLC-Q-Exactive Plus MS. Results:: The total radioactivity of the study drug in rat plasma rapidly declined with an average terminal elimination half-life of 0.35 h. The radioactivity in most tissues reached the maximum concentration at 0.25 h post-- dosing. The radioactivity is mainly concentrated in the kidney and pancreas. The drug-related substances tended to be distributed into the blood cells in the circulation. At 168 h post dosing, the mean recovery of the total radioactivity in urine and feces was 78.82%. Fecal excretion was the major excretion route, accounting for approximately 61% of the radioactive dose. The study drug was metabolized extensively, and a total of 17 metabolites were identified in rat plasma, urine, and feces. The major metabolic pathways involved oxidation, oxidation and dehydrogenation, and O-dephenylation. result: The total radioactivity of the study drug in rat plasma rapidly declined with an average terminal elimination half-life of 0.19 h. The radioactivity in most tissues reached the maximum concentration at 0.25 h post dosing. The radioactivity mainly concentrated in the kidney and pancreas. The drug-related substances tended to be distributed into the blood cells in the circulation. At 168 h post dosing, the mean recovery of the total radioactivity in urine and feces was 78.82%. Fecal excretion was the major excretion route, accounting for approximately 61% of the radioactive dose. The study drug was metabolized extensively and a total of 17 metabolites were identified in rat plasma, urine, and feces. The major metabolic pathways involved oxidation, oxidation and dehydrogenation, and O-dephenylation. There was no significant sex difference in the distribution, metabolism and excretion of [14C]101BHG-D01. Conclusion:: In conclusion, the study results are useful for better understanding the pharmacokinetic profiles of 101BHG-D01 and provide a robust foundation for subsequent clinical studies.","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"5 1","pages":""},"PeriodicalIF":2.3,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138576480","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}
{"title":"Meet the Editorial Board Member","authors":"Ramesh Jayaraman","doi":"10.2174/138920022404230714101907","DOIUrl":"https://doi.org/10.2174/138920022404230714101907","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136119852","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}
{"title":"Meet the Associate Editor","authors":"Hiroshi Yamazaki","doi":"10.2174/138920022408230928105612","DOIUrl":"https://doi.org/10.2174/138920022408230928105612","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135053971","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}
{"title":"Meet the Editorial Board Member","authors":"Mohammad A. Kamal","doi":"10.2174/138920022407230928095028","DOIUrl":"https://doi.org/10.2174/138920022407230928095028","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135855890","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}
{"title":"Meet the Editorial Board Member","authors":"Tadatoshi Tanino","doi":"10.2174/138920022406230908104733","DOIUrl":"https://doi.org/10.2174/138920022406230908104733","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"256 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135145412","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}
{"title":"Meet the Editorial Board Member","authors":"Upendra A. Argikar","doi":"10.2174/138920022405230824123727","DOIUrl":"https://doi.org/10.2174/138920022405230824123727","url":null,"abstract":"","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135517256","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}
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