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Itraconazole Bioequivalence Revisited: Influence of Gender on Highly Variable Drugs 伊曲康唑生物等效性重访:性别对高度可变药物的影响

The open drug metabolism journal Pub Date : 2007-12-18 DOI: 10.2174/1874073100701010007

P. Fagiolino, Nicolás González, M. Vázquez, R. Eiraldi

{"title":"Itraconazole Bioequivalence Revisited: Influence of Gender on Highly Variable Drugs","authors":"P. Fagiolino, Nicolás González, M. Vázquez, R. Eiraldi","doi":"10.2174/1874073100701010007","DOIUrl":"https://doi.org/10.2174/1874073100701010007","url":null,"abstract":"Highly variable drugs have been defined as drugs with a residual variability of more than 30% in terms of the ANOVA coefficient of variation. Different approaches have been proposed during the last years to deal with this problem but the topic remains controversial. Itraconazole, a highly variable drug, has low bioavailability with a high CYP3A4 presystemic biotransformation. Also, it has a very poor aqueous solubility which is very dependent on the pH of the dissolution medium. The pregnane X receptor (PXR) has been shown to mediate the genomic effects of progesterone and estradiol in the expression of the cytochrome P-450 gene family, which plays an important role in the metabolism of hormones and xenobiotics. During the menstrual cycle both hormone concentrations vary, providing a rationale for the more variable CYP3A4 activity in women. The analysis of the data of an itraconazole bioequivalence study involving 24 healthy volunteers (12 men and 12 women) carried out by other investigators enables us to conclude that women have less oral bioavailability and more variable AUC than men. Low bioavailability seems to be related with the higher stomach pH observed in women and variability with the aforementioned menstrual cycle incidence on both pH and CYP3A4 expression. The lower variability observed in men made it possible to discriminate differences in AUC’s variability displayed by each brand.","PeriodicalId":89636,"journal":{"name":"The open drug metabolism journal","volume":"1 1","pages":"7-13"},"PeriodicalIF":0.0,"publicationDate":"2007-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Novel Role of Soluble Epoxide Hydrolase in Regulating Cholesterol in Mammalian Cells. 可溶性环氧化物水解酶在调节哺乳动物细胞胆固醇中的新作用。

The open drug metabolism journal Pub Date : 2007-01-01 DOI: 10.2174/1874073100701010001

Ahmed Enayetallah, Li Cao, David F Grant

{"title":"Novel Role of Soluble Epoxide Hydrolase in Regulating Cholesterol in Mammalian Cells.","authors":"Ahmed Enayetallah, Li Cao, David F Grant","doi":"10.2174/1874073100701010001","DOIUrl":"10.2174/1874073100701010001","url":null,"abstract":"<p><p>Soluble epoxide hydrolase (sEH) is becoming an attractive therapeutic target in cardiovascular disease. Recently, known human sEH polymorphisms were associated with elevated plasma cholesterol and atherosclerosis. In this study we evaluated the potential role of sEH in regulating cholesterol metabolism through modulating the levels of fatty acid epoxide substrates and/or their corresponding diol products known to activate peroxisome proliferator activated receptors (PPARs). We measured changes in cholesterol levels induced by expressing sEH proteins in mammalian cell lines and in response to treatment with various sEH-related compounds. Our results indicate that sEH has a cholesterol lowering effect that is mediated at least in part through its C-terminal hydrolase activity. In addition, several fatty acid epoxides and their corresponding diols showed cholesterol lowering effects in the current study. In conclusion, this study provides evidence that fatty acid epoxides and diols are endogenous cholesterol lowering molecules and that sEH may be involved in cholesterol regulation by modulating their levels.</p>","PeriodicalId":89636,"journal":{"name":"The open drug metabolism journal","volume":"1 ","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349169/pdf/nihms358886.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30614148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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