Biopharmaceutics & Drug Disposition最新文献_第9页

Febuxostat and its major acyl glucuronide metabolite are potent inhibitors of organic anion transporter 3: Implications for drug-drug interactions with rivaroxaban 非布司他及其主要的酰基葡萄糖醛酸代谢物是有机阴离子转运体的有效抑制剂3:与利伐沙班药物相互作用的意义

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2022-01-27 DOI: 10.1002/bdd.2310

Lloyd Wei Tat Tang, Tino Woon Huai Cheong, Eric Chun Yong Chan

{"title":"Febuxostat and its major acyl glucuronide metabolite are potent inhibitors of organic anion transporter 3: Implications for drug-drug interactions with rivaroxaban","authors":"Lloyd Wei Tat Tang, Tino Woon Huai Cheong, Eric Chun Yong Chan","doi":"10.1002/bdd.2310","DOIUrl":"10.1002/bdd.2310","url":null,"abstract":"Febuxostat is a second-line xanthine oxidase inhibitor that undergoes extensive hepatic metabolism to yield its major acyl-β-D-glucuronide metabolite (febuxostat AG). It was recently reported that febuxostat inhibited organic anion transporter 3 (OAT3)-mediated uptake of enalaprilat. Here, we investigated the inhibition of febuxostat and febuxostat AG on OAT3 in transfected human embryonic kidney 293 cells. Our transporter inhibition assays confirmed the potent noncompetitive and competitive inhibition of OAT3-mediated estrone-3-sulfate transport by febuxostat and febuxostat AG with corresponding apparent Ki values of 0.55 and 6.11 μM respectively. After accounting for probe substrate-dependency and protein binding effects, mechanistic static modelling with the direct factor Xa anticoagulant rivaroxaban estimated a 1.47-fold increase in its systemic exposure when co-administered with febuxostat based on OAT3 interaction which in turn exacerbates the bleeding risk from baseline for patients with atrial fibrillation by 1.51-fold. Taken together, our results suggested that the concomitant usage of febuxostat with rivaroxaban may potentially culminate in a clinically-significant drug-drug interaction and result in an increased risk of bleeding as a result of its OAT3 inhibition.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"43 2","pages":"57-65"},"PeriodicalIF":2.1,"publicationDate":"2022-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39867351","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: 1

In vitro and in silico interactions of antiulcer, glucocorticoids and urological drugs on human carbonic anhydrase I and II isozymes 抗溃疡、糖皮质激素和泌尿科药物对人碳酸酐酶I和II同工酶的体外和体内相互作用

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2022-01-26 DOI: 10.1002/bdd.2309

Uğur Güller, Şükrü Beydemir, Ömer İrfan Küfrevioğlu

{"title":"In vitro and in silico interactions of antiulcer, glucocorticoids and urological drugs on human carbonic anhydrase I and II isozymes","authors":"Uğur Güller, Şükrü Beydemir, Ömer İrfan Küfrevioğlu","doi":"10.1002/bdd.2309","DOIUrl":"10.1002/bdd.2309","url":null,"abstract":"Carbonic anhydrases (CAs, Enzyme Commission 4.2.1.1) convert carbon dioxide to bicarbonate in metabolism and use Zn2+ ions as a cofactor for their catalytic activity. The activators or inhibitors of CA-I and CA-II, which are the most abundant CA isozymes in erythrocytes, have pharmacological applications in medicine. So, investigation of drug-protein interaction of these isozymes is significant. On this basis, the objective of this study was to clarify the primer effects of widely used drugs on the activity of human CA-I and CA-II enzymes and elucidate the inhibition mechanism through molecular docking studies. For this aim isozymes were purified from human erythrocytes by affinity chromatography technique. Then inhibition profiles of antiulcer, glucocorticoids, and urological drugs were investigated. As a result, while budesonide had the highest inhibitory potency on hydratase activity of hCA-I with the IC50 of 0.08 mM, levofloxacin showed the highest inhibition effect on hCA-II with the IC50 of 0.886 mM. The most effective inhibitor on the esterase activity of isozymes was found as fluticasone propionate with the Ki values of 0.0365 ± 0.016 mM and 0.054 ± 0.018 mM respectively. However, by molecular docking study, it was estimated that budesonide showed maximum inhibition potency for both isozymes with the free binding energy of −7.58 and −6.97 kcal/mol, respectively. Consequently, it was observed that some of the drugs studied did not show any inhibitory effect. Drug-enzyme interactions were also estimated by molecular docking. This study could contribute to the discovery of new drug candidates and as well as target proteins.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"43 2","pages":"47-56"},"PeriodicalIF":2.1,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39963741","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: 3

Influence of piperine and omeprazole on the regional absorption of Daclatasvir from rabbit intestine 胡椒碱和奥美拉唑对达卡他韦兔肠局部吸收的影响

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2022-01-07 DOI: 10.1002/bdd.2308

Shimaa M. Ashmawy, Dina A. Eltahan, Mohamed A. Osman, Ebtessam A. Essa

{"title":"Influence of piperine and omeprazole on the regional absorption of Daclatasvir from rabbit intestine","authors":"Shimaa M. Ashmawy, Dina A. Eltahan, Mohamed A. Osman, Ebtessam A. Essa","doi":"10.1002/bdd.2308","DOIUrl":"10.1002/bdd.2308","url":null,"abstract":"The study assessed the site dependent intestinal absorption of Daclatasvir and investigated the effects of piperine and omeprazole on such absorption utilizing in situ rabbit intestinal perfusion technique. The intestinal absorption of Daclatasvir was assessed in four segments: duodenum, jejunum, ileum, and colon. The effect of co-perfusion with omeprazole was monitored through the tested anatomical sites. The effect of piperine, a P-glycoprotein (P-gp) inhibitor on Daclatasvir absorption from jejunum and ileum was tested. The results showed that Daclatasvir was incompletely absorbed from the rabbit small and large intestine. The absorptive clearance per unit length (PeA/L) was site dependent and was ranked as colon > duodenum > jejunum > ileum. This rank is the opposite of the rank of P-gp intestinal content suggesting possible influence for P-gp. Co-perfusion with omeprazole increased PeA/L and this was evidenced also with reduced the L95% of Daclatasvir from both small and large intestinal segments. Significant enhancement in Daclatasvir absorption through jejunum and ileum was shown in presence of piperine. Daclatasvir showed site dependent intestinal absorption in a manner suggesting its affection by P-gp efflux. This effect was inhibited by piperine. Co-administration of Daclatasvir with omeprazole can enhance intestinal absorption a phenomenon which requires extension to human pharmacokinetic investigation.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"43 1","pages":"33-44"},"PeriodicalIF":2.1,"publicationDate":"2022-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39795447","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

Evaluation of sex differences in the pharmacokinetics of oral sumatriptan in healthy Korean subjects using population pharmacokinetic modeling 使用群体药代动力学模型评估健康韩国受试者口服舒马匹坦药代动力学的性别差异

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-19 DOI: 10.1002/bdd.2307

Boram Ohk, Sookjin Seong, Joomi Lee, Miri Gwon, Wooyoul Kang, Haewon Lee, Youngran Yoon, Heedoo Yoo

{"title":"Evaluation of sex differences in the pharmacokinetics of oral sumatriptan in healthy Korean subjects using population pharmacokinetic modeling","authors":"Boram Ohk, Sookjin Seong, Joomi Lee, Miri Gwon, Wooyoul Kang, Haewon Lee, Youngran Yoon, Heedoo Yoo","doi":"10.1002/bdd.2307","DOIUrl":"10.1002/bdd.2307","url":null,"abstract":"Sumatriptan was introduced in 1983, as the first of the triptans, selective 5-hydroxytryptamine (5-HT1B/1D) receptor agonists, to treat moderate to severe migraine. Migraine predominates in females. Although there have been reports of sex differences in migraine-associated features and pharmacokinetics (PKs) of some triptans, sex differences in the PKs of oral sumatriptan have never been evaluated in Korean. We conducted this study of oral sumatriptan to assess the sex differences in Korean population. Thirty-eight healthy Korean subjects who participated in two separate clinical studies receiving a single oral dose of 50 mg sumatriptan with the same protocols were included in this analysis. A total of 532 sumatriptan concentration observations were used for a population PK modeling. Validation of final population PK model of sumatriptan was performed using bootstrap and visual predictive check. The PK profile of oral sumatriptan was adequately described by a one-compartmental model with combined transit compartment model and a first-order absorption. The covariate analysis showed that the clearance of oral sumatriptan was significantly higher in males than in females (male: 444 L/h, female: 281 L/h). Our results showed that there were sex differences in the clearance of oral sumatriptan. These results encourage further studies to establish the sumatriptan pharmacokinetic–pharmacodynamic model considering sex-related PK differences, which may help to determine optimal dosing regimens for effective treatment of migraine in males and females. Clinical trial registration: CRIS Registration No. KCT0001784.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"43 1","pages":"23-32"},"PeriodicalIF":2.1,"publicationDate":"2021-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/5b/BDD-43-23.PMC9306698.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39737441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC-MS/MS 用UPLC-MS/MS测定黄腐酚在大鼠体内的吸收、代谢和药动学特征

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-16 DOI: 10.1002/bdd.2306

Huan-Huan Bai, Tian-Shuang Xia, Yi-Ping Jiang, Wu-Mu Xu, Ping-Cui Xu, Na-Ni Wang, Xiao-Jun Gou, Hai-Liang Xin

{"title":"Absorption, metabolism, and pharmacokinetic profile of xanthohumol in rats as determined via UPLC-MS/MS","authors":"Huan-Huan Bai, Tian-Shuang Xia, Yi-Ping Jiang, Wu-Mu Xu, Ping-Cui Xu, Na-Ni Wang, Xiao-Jun Gou, Hai-Liang Xin","doi":"10.1002/bdd.2306","DOIUrl":"10.1002/bdd.2306","url":null,"abstract":"Xanthohumol, a natural isoflavone from Humulus lupulus L., possesses biological activities. However, the biological fate of xanthohumol in vivo remains unclear. The aim of this study was to investigate the absorption and metabolism of xanthohumol in rats through UPLC-MS/MS. The plasma, urine and fecal samples were collected after oral administration of xanthohumol (25, 50, 100 mg/kg) in SD rats. The contents of xanthohumol and its metabolites were determined by UPLC-MS/MS. A total of 6 metabolites of xanthohumol were identified in rats, including methylated, glucuronidated, acid-catalyzed cyclization and oxidation, indicating xanthohumol underwent phase I and II metabolism. Besides, isoxanthohumol was the major metabolites of xanthohumol. Xanthohumol was rapidly absorbed, metabolized, and eliminated in rats. The pharmacokinetics results showed the Tmax of xanthohumol and isoxanthohumol were 3 and 2.33 h, respectively. The AUC0−t of xanthohumol and isoxanthohumol were 138.83 ± 6.03 and 38.77 ± 4.46 ng/ml·h, respectively. Furthermore, xanthohumol was mainly excreted in the form of prototype through feces and a small amount of xanthohumol was excreted through urine. These results illustrated the absorption, metabolism, and pharmacokinetics process of xanthohumol in rats, and provided a reference for the further rational applications.","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"43 1","pages":"11-22"},"PeriodicalIF":2.1,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39819228","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: 1

Regulatory Biopharmaceutics 监管生物药剂学

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-10 DOI: 10.1002/9781119678366.ch10

S. Budhdeo, P. Dickinson, T. Flanagan

引用次数: 0

Special Populations 特殊人群

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-10 DOI: 10.1002/9781119678366.ch13

Christine M. Madla, Francesca K. H. Gavins, Sarah J Trenfield, Abdul W. Basit

引用次数: 0

Biopharmaceutics to Inform Candidate Drug Selection and Optimisation 生物制药为候选药物的选择和优化提供信息

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-10 DOI: 10.1002/9781119678366.ch7

Linette Ruston

引用次数: 0

An Introduction to Biopharmaceutics 生物制药导论

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-10 DOI: 10.1002/9781119678366.ch1

H. Batchelor

引用次数: 0

Dissolution 解散

IF 2.1 4区医学

Biopharmaceutics & Drug Disposition Pub Date : 2021-12-10 DOI: 10.1002/9781119678366.ch6

H. Batchelor, J. Butler

引用次数: 0