Synthesis and evaluation of indomethacin prodrugs with a diester structure that are metabolically activated by human carboxylesterases
In this study, by changing the structure of the prodrug to a diester structure, it was found that CES2 activity was equivalent to CES1 activity.It should be noted that the use of diester prodrugs in prodrug discovery, where organ-specific hydrolysis reactions are expected, may not yield the expected results.PMID:38142303 | DOI:10.1080/00498254.2023.2298270 (Source: Xenobiotica)
Source: Xenobiotica - December 24, 2023 Category: Research Authors: Daisuke Takani Masato Takahashi Masakiyo Hosokawa Source Type: research
Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies
Xenobiotica. 2023 Dec 18:1-13. doi: 10.1080/00498254.2023.2292725. Online ahead of print.ABSTRACTThe pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxicity.Preclinical studies require time and resources and are prone to error. Moreover, according to the United States Food and Drug Administration Modernisation Act 2, animal testing is no longer mandatory for new drug development, and an animal-free alternative, such as cell-based assay and computer models, can be used.Different physio...
Source: Xenobiotica - December 19, 2023 Category: Research Authors: Gobardhan Bal Lakshmi Kanakaraj Bibhash Chandra Mohanta Source Type: research
Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies
Xenobiotica. 2023 Dec 18:1-13. doi: 10.1080/00498254.2023.2292725. Online ahead of print.ABSTRACTThe pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxicity.Preclinical studies require time and resources and are prone to error. Moreover, according to the United States Food and Drug Administration Modernisation Act 2, animal testing is no longer mandatory for new drug development, and an animal-free alternative, such as cell-based assay and computer models, can be used.Different physio...
Source: Xenobiotica - December 19, 2023 Category: Research Authors: Gobardhan Bal Lakshmi Kanakaraj Bibhash Chandra Mohanta Source Type: research
Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies
Xenobiotica. 2023 Dec 18:1-13. doi: 10.1080/00498254.2023.2292725. Online ahead of print.ABSTRACTThe pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxicity.Preclinical studies require time and resources and are prone to error. Moreover, according to the United States Food and Drug Administration Modernisation Act 2, animal testing is no longer mandatory for new drug development, and an animal-free alternative, such as cell-based assay and computer models, can be used.Different physio...
Source: Xenobiotica - December 19, 2023 Category: Research Authors: Gobardhan Bal Lakshmi Kanakaraj Bibhash Chandra Mohanta Source Type: research
Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies
Xenobiotica. 2023 Dec 18:1-13. doi: 10.1080/00498254.2023.2292725. Online ahead of print.ABSTRACTThe pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxicity.Preclinical studies require time and resources and are prone to error. Moreover, according to the United States Food and Drug Administration Modernisation Act 2, animal testing is no longer mandatory for new drug development, and an animal-free alternative, such as cell-based assay and computer models, can be used.Different physio...
Source: Xenobiotica - December 19, 2023 Category: Research Authors: Gobardhan Bal Lakshmi Kanakaraj Bibhash Chandra Mohanta Source Type: research
Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies
Xenobiotica. 2023 Dec 18:1-13. doi: 10.1080/00498254.2023.2292725. Online ahead of print.ABSTRACTThe pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxicity.Preclinical studies require time and resources and are prone to error. Moreover, according to the United States Food and Drug Administration Modernisation Act 2, animal testing is no longer mandatory for new drug development, and an animal-free alternative, such as cell-based assay and computer models, can be used.Different physio...
Source: Xenobiotica - December 19, 2023 Category: Research Authors: Gobardhan Bal Lakshmi Kanakaraj Bibhash Chandra Mohanta Source Type: research
CYP-catalysed Cycling of Clozapine and Clozapine- < em > N < /em > -oxide Promotes the Generation of Reactive Oxygen Species < em > in vitro < /em >
This study aimed to investigate the contribution of selected CYP isoforms to cycling between clozapine and its major circulating metabolites, N-desmethylclozapine and clozapine-N-oxide, with the potential for reactive species production. CYP supersome™-based in vitro techniques were utilised to quantify specific enzyme activity associated with clozapine, clozapine-N-oxide and N-desmethylclozapine metabolism. The formation of reactive species within each incubation were quantified, and known intermediates detected. CYP3A4 predominately catalysed clozapine-N-oxide formation from clozapine and was associated with concentrat...
Source: Xenobiotica - December 18, 2023 Category: Research Authors: Ellen Kingston Malcolm Tingle Brandi L Bellissima Nuala Helsby Kathryn Burns Source Type: research
Through a computer monitor darkly: artificial intelligence in absorption, distribution, metabolism and excretion science
Xenobiotica. 2023 Dec 14:1-15. doi: 10.1080/00498254.2023.2295361. Online ahead of print.ABSTRACTArtificial Intelligence (AI) is poised or has already begun to influence highly absorption, distribution, metabolism and excretion (ADME) science. It is not in the area expected, that of superior modelling of ADME data to increase its predictive power. It is influencing traditional exhaustive and careful literature research by providing almost perfect summaries of existing information. This will highly influence how people study, graduate and progress in the ADME sciences. The literature contains many flaws, protein binding inf...
Source: Xenobiotica - December 14, 2023 Category: Research Authors: Dennis A Smith Lucy Melanie Burton Sophie Amanda Source Type: research
Through a computer monitor darkly: artificial intelligence in absorption, distribution, metabolism and excretion science
Xenobiotica. 2023 Dec 14:1-15. doi: 10.1080/00498254.2023.2295361. Online ahead of print.ABSTRACTArtificial Intelligence (AI) is poised or has already begun to influence highly absorption, distribution, metabolism and excretion (ADME) science. It is not in the area expected, that of superior modelling of ADME data to increase its predictive power. It is influencing traditional exhaustive and careful literature research by providing almost perfect summaries of existing information. This will highly influence how people study, graduate and progress in the ADME sciences. The literature contains many flaws, protein binding inf...
Source: Xenobiotica - December 14, 2023 Category: Research Authors: Dennis A Smith Lucy Melanie Burton Sophie Amanda Source Type: research
Through a computer monitor darkly: artificial intelligence in absorption, distribution, metabolism and excretion science
Xenobiotica. 2023 Dec 14:1-15. doi: 10.1080/00498254.2023.2295361. Online ahead of print.ABSTRACTArtificial Intelligence (AI) is poised or has already begun to influence highly absorption, distribution, metabolism and excretion (ADME) science. It is not in the area expected, that of superior modelling of ADME data to increase its predictive power. It is influencing traditional exhaustive and careful literature research by providing almost perfect summaries of existing information. This will highly influence how people study, graduate and progress in the ADME sciences. The literature contains many flaws, protein binding inf...
Source: Xenobiotica - December 14, 2023 Category: Research Authors: Dennis A Smith Lucy Melanie Burton Sophie Amanda Source Type: research
Through a computer monitor darkly: artificial intelligence in absorption, distribution, metabolism and excretion science
Xenobiotica. 2023 Dec 14:1-15. doi: 10.1080/00498254.2023.2295361. Online ahead of print.ABSTRACTArtificial Intelligence (AI) is poised or has already begun to influence highly absorption, distribution, metabolism and excretion (ADME) science. It is not in the area expected, that of superior modelling of ADME data to increase its predictive power. It is influencing traditional exhaustive and careful literature research by providing almost perfect summaries of existing information. This will highly influence how people study, graduate and progress in the ADME sciences. The literature contains many flaws, protein binding inf...
Source: Xenobiotica - December 14, 2023 Category: Research Authors: Dennis A Smith Lucy Melanie Burton Sophie Amanda Source Type: research
Effect of Genetic Polymorphisms on the Pharmacokinetics of Gefitinib in Healthy Chinese Volunteers
Xenobiotica. 2023 Dec 12:1-28. doi: 10.1080/00498254.2023.2294039. Online ahead of print.ABSTRACTGefitinib is the first generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolized by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were admimistered a single dose of gefitinib and the blood samples were used for quantifyin...
Source: Xenobiotica - December 12, 2023 Category: Research Authors: Ying-Rong Chen Xiang Yu Li-Min Xu Jue Mei Meng-Li Tian Min Xu Qiu-Yue Jin Li-Bing Ye Shui-Xin Yang Source Type: research
Effect of Genetic Polymorphisms on the Pharmacokinetics of Gefitinib in Healthy Chinese Volunteers
Xenobiotica. 2023 Dec 12:1-28. doi: 10.1080/00498254.2023.2294039. Online ahead of print.ABSTRACTGefitinib is the first generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolized by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). In the present study, the pharmacokinetics of gefitinib in healthy Chinese volunteers was investigated and the effect of genetic polymorphisms on its variability was evaluted.Forty-five healthy volunteers were admimistered a single dose of gefitinib and the blood samples were used for quantifyin...
Source: Xenobiotica - December 12, 2023 Category: Research Authors: Ying-Rong Chen Xiang Yu Li-Min Xu Jue Mei Meng-Li Tian Min Xu Qiu-Yue Jin Li-Bing Ye Shui-Xin Yang Source Type: research
Novel application of PBBM to justify impact of faster dissolution on safety and pharmacokinetics - a case study and utility in regulatory justifications
Xenobiotica. 2023 Dec 7:1-16. doi: 10.1080/00498254.2023.2289160. Online ahead of print.ABSTRACTPhysiologically based biopharmaceutics modelling (PBBM) was recognised as potential approach for biopharmaceutics applications. However, PBBM to justify safety is an unexplored area.In this manuscript, we elucidated PBBM application for safety justification. Product DRL is a generic extended release tablet containing an anti-epileptic narrow therapeutic index (NTI) drug. During dossier review, regulatory agency requested to evaluate the impact of faster dissolution profiles observed during stability on safety aspects. In order t...
Source: Xenobiotica - December 8, 2023 Category: Research Authors: Rajkumar Boddu Sivacharan Kollipara Adithya Karthik Bhattiprolu Tausif Ahmed Source Type: research
Novel application of PBBM to justify impact of faster dissolution on safety and pharmacokinetics - a case study and utility in regulatory justifications
Xenobiotica. 2023 Dec 7:1-16. doi: 10.1080/00498254.2023.2289160. Online ahead of print.ABSTRACTPhysiologically based biopharmaceutics modelling (PBBM) was recognised as potential approach for biopharmaceutics applications. However, PBBM to justify safety is an unexplored area.In this manuscript, we elucidated PBBM application for safety justification. Product DRL is a generic extended release tablet containing an anti-epileptic narrow therapeutic index (NTI) drug. During dossier review, regulatory agency requested to evaluate the impact of faster dissolution profiles observed during stability on safety aspects. In order t...
Source: Xenobiotica - December 8, 2023 Category: Research Authors: Rajkumar Boddu Sivacharan Kollipara Adithya Karthik Bhattiprolu Tausif Ahmed Source Type: research
