{"title":"食物对以胆汁盐为辅剂的依达拉奉无定形分散剂口服药代动力学的影响--第二部分。","authors":"Dhrumi Patel, Sarika Wairkar","doi":"10.1016/j.pharma.2024.06.005","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions.</p><p><strong>Methods: </strong>The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma.</p><p><strong>Results: </strong>The results suggested that EDR COAM did not show a significant difference in C<sub>max</sub> (P=0.3544) and AUC (P=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced C<sub>max</sub> (P<0.0001) and AUC (P=0.0094) in the fed condition, respectively. The C<sub>max</sub> and AUC of EDR COAM were improved in fasted (AUC: 2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food.</p><p><strong>Conclusions: </strong>The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.</p>","PeriodicalId":8332,"journal":{"name":"Annales pharmaceutiques francaises","volume":null,"pages":null},"PeriodicalIF":1.0000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of food on oral pharmacokinetics of edaravone coamorphous dispersion containing bile salts as coformers - Part II.\",\"authors\":\"Dhrumi Patel, Sarika Wairkar\",\"doi\":\"10.1016/j.pharma.2024.06.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions.</p><p><strong>Methods: </strong>The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma.</p><p><strong>Results: </strong>The results suggested that EDR COAM did not show a significant difference in C<sub>max</sub> (P=0.3544) and AUC (P=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced C<sub>max</sub> (P<0.0001) and AUC (P=0.0094) in the fed condition, respectively. The C<sub>max</sub> and AUC of EDR COAM were improved in fasted (AUC: 2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food.</p><p><strong>Conclusions: </strong>The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.</p>\",\"PeriodicalId\":8332,\"journal\":{\"name\":\"Annales pharmaceutiques francaises\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2024-06-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annales pharmaceutiques francaises\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.pharma.2024.06.005\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annales pharmaceutiques francaises","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.pharma.2024.06.005","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Effect of food on oral pharmacokinetics of edaravone coamorphous dispersion containing bile salts as coformers - Part II.
Objectives: Edaravone (EDR) is an effective neuroprotective agent in various neurological diseases; however, its use is restricted due to poor oral absorption. Bile salts are known for improving solubility and inhibiting drug crystallization in supersaturated conditions of the gastrointestinal tract (GIT). In our previous work, we prepared coamorphous dispersion (COAM) of EDR with sodium taurocholate (NaTC) using spray drying. The optimized EDR COAM exhibited superior in vitro performance compared to plain EDR. EDR is well absorbed in fasted-over-fed conditions.
Methods: The present work, we conducted a pharmacokinetic study for EDR and EDR COAM in fasted and fed conditions to check effect of food on its oral absorption. The LC-MS/MS-based method was developed and validated to determine the amount of EDR in plasma.
Results: The results suggested that EDR COAM did not show a significant difference in Cmax (P=0.3544) and AUC (P=0.1696) of fasted and fed states. On the other hand, plain EDR showed 2-fold and 3-fold reduced Cmax (P<0.0001) and AUC (P=0.0094) in the fed condition, respectively. The Cmax and AUC of EDR COAM were improved in fasted (AUC: 2.56-fold) and fed states (AUC: 5.74-fold) than plain EDR, suggesting better oral absorption of COAM than crystalline EDR without having the effect of food.
Conclusions: The unique structural attributes of NaTC had the potential to inhibit the recrystallization of EDR in GIT, while concurrently reducing the impact of food on the oral absorption of EDR.
期刊介绍:
This journal proposes a scientific information validated and indexed to be informed about the last research works in all the domains interesting the pharmacy. The original works, general reviews, the focusing, the brief notes, subjected by the best academics and the professionals, propose a synthetic approach of the last progress accomplished in the concerned sectors. The thematic Sessions and the – life of the Academy – resume the communications which, presented in front of the national Academy of pharmacy, are in the heart of the current events.