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https://www.readbyqxmd.com/read/27904436/effects-of-metformin-on-blood-and-urine-pro-inflammatory-mediators-in-patients-with-type-2-diabetes
#1
Wei Chen, Xiaojie Liu, Shandong Ye
BACKGROUND: Metformin has been used for the treatment of type 2 diabetes by suppressing hepatic gluconeogenesis. It has been shown that the subclinical inflammatory responses play important roles in the pathogenesis of type 2 diabetes. In the present study, we determined the effects of metformin on the levels of pro-inflammatory cytokines (i.e., IL-6, TNF-α, and MCP-1) and anti-inflammatory mediator IL-10 in blood and urine of patients with type 2 diabetes. There were 210 patients with type 2 diabetes, which were randomized into metformin (n = 112) and non-metformin (gliclazide, acarbose, and repaglinide, n = 98) groups...
2016: Journal of Inflammation
https://www.readbyqxmd.com/read/27862160/in-vitro-and-pbpk-based-assessment-of-drug-drug-interaction-potential-of-canagliflozin
#2
Rao N V S Mamidi, Shannon Dallas, Carlo Sensenhauser, Heng Keang Lim, Ellen Scheers, Peter Verboven, Filip Cuyckens, Laurent Leclercq, David C Evans, Michael F Kelley, Mark D Johnson, Jan Snoeys
AIMS: Canagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed. METHODS: DDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transporters. Basic predictive approaches were applied to determine potential interaction in vivo. A physiologically-based pharmacokinetic (PBPK) model was developed and clinical DDI simulations were performed to determine the likelihood of CYP inhibition by canagliflozin...
November 11, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27857189/a-variation-in-kcnq1-gene-is-associated-with-repaglinide-efficacy-on-insulin-resistance-in-chinese-type-2-diabetes-mellitus-patients
#3
Xueyan Zhou, Jing Zhu, Zejun Bao, Zhenhai Shang, Tao Wang, Jinfang Song, Juan Sun, Wei Li, Temitope Isaac Adelusi, Yan Wang, Dongmei Lv, Qian Lu, Xiaoxing Yin
Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27769931/development-of-repaglinide-microspheres-using-novel-acetylated-starches-of-bitter-and-chinese-yams-as-polymers
#4
Adenike Okunlola, Amusa Sarafadeen Adebayo, Moji Christianah Adeyeye
Tropical starches from Dioscorea dumetorum (bitter) and Dioscorea oppositifolia (Chinese) yams were acetylated with acetic anhydride in pyridine medium and utilized as polymers for the delivery of repaglinide in microsphere formulations in comparison to ethyl cellulose. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. Acetylation was confirmed by FTIR, (1)H NMR spectroscopy. A 3(2) factorial experimental design was performed using polymer type and drug-polymer ratio as independent variables...
October 18, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27734142/a-liquid%C3%A2-chromatography-tandem-mass-spectrometry-analysis-of-nine-cytochrome-p450-probe-drugs-and-their-corresponding-metabolites-in-human-serum-and-urine
#5
Elena Puris, Markku Pasanen, Mikko Gynther, Merja R Häkkinen, Jussi Pihlajamäki, Tapani Keränen, Paavo Honkakoski, Hannu Raunio, Aleksanteri Petsalo
Cocktail phenotyping using specific probe drugs for cytochrome P450 (CYP) enzymes provides information on the real-time activity of multiple CYPs. We investigated different sample preparation techniques and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple protein precipitation for the analysis of nine CYP probe drugs and their metabolites in human serum and urine. Specific CYP probe drugs (melatonin, CYP1A2; nicotine, CYP2A6; bupropion, CYP2B6; repaglinide, CYP2C8; losartan, CYP2C9; omeprazole, CYP2C19 and CYP3A4; dextromethorphan, CYP2D6; chlorzoxazone, CYP2E; midazolam, CYP3A4) and their main metabolites, with the exception of 3'-hydroxyrepaglinide, were quantified in human serum and urine using the developed LC-MS/MS method...
October 12, 2016: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/27665059/drug-drug-interactions-between-immunosuppressants-and-antidiabetic-drugs-in-the-treatment-of-post-transplant-diabetes-mellitus
#6
Thomas Vanhove, Quinten Remijsen, Dirk Kuypers, Pieter Gillard
Post-transplant diabetes mellitus is a frequent complication of solid organ transplantation that generally requires treatment with lifestyle interventions and antidiabetic medication. A number of demonstrated and potential pharmacokinetic drug-drug interactions (DDIs) exist between commonly used immunosuppressants and antidiabetic drugs, which are comprehensively summarized in this review. Cyclosporine (CsA) itself inhibits the cytochrome P450 (CYP) 3A4 enzyme and a variety of drug transporters. As a result, it increases exposure to repaglinide and sitagliptin, will likely increase the exposure to nateglinide, glyburide, saxagliptin, vildagliptin and alogliptin, and could theoretically increase the exposure to gliquidone and several sodium-glucose transporter (SGLT)-2 inhibitors...
September 14, 2016: Transplantation Reviews
https://www.readbyqxmd.com/read/27659712/clinical-and-molecular-characterization-of-a-novel-ins-mutation-identified-in-patients-with-mody-phenotype
#7
Barbara Piccini, Rosangela Artuso, Lorenzo Lenzi, Monica Guasti, Giulia Braccesi, Federica Barni, Emilio Casalini, Sabrina Giglio, Sonia Toni
Correct diagnosis of Maturity-Onset Diabetes of the Young (MODY) is based on genetic tests requiring an appropriate subject selection by clinicians. Mutations in the insulin (INS) gene rarely occur in patients with MODY. This study is aimed at determining the genetic background and clinical phenotype in patients with suspected MODY. 34 patients with suspected MODY, negative for mutations in the GCK, HNF1α, HNF4α, HNF1β and PDX1 genes, were screened by next generation sequencing (NGS). A heterozygous INS mutation was identified in 4 members of the same family...
September 19, 2016: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/27647480/efficacy-and-safety-of-repaglinide-added-to-sitagliptin-in-japanese-patients-with-type-2-diabetes-a-randomized-24-week-open-label-clinical-trial
#8
Akihiro Nishimura, Shuki Usui, Naoki Kumashiro, Hiroshi Uchino, Azusa Yamato, Daijiro Yasuda, Kaoru Nagasawa, Minoru Okubo, Yasumichi Mori, Takahisa Hirose
Although sitagliptin and repaglinide monotherapies improve postprandial hyperglycemia, the long-term effects and safety of their combination has not been examined. In this randomized 24-week trial of Japanese patients with poor control (HbA1c 7.0-8.5%) by sitagliptin, we divided 40 patients randomly into two equal groups of the repaglinide add-on to sitagliptin (ADD-ON, n=20), or sitagliptin switched to repaglinide (SWITCH, n=20). The meal tolerance test was carried out at weeks 0 and 24. The primary outcomes were changes in HbA1c and area under the curves (AUC) of glucose from the baseline to week 24...
September 17, 2016: Endocrine Journal
https://www.readbyqxmd.com/read/27635199/antioxidant-properties-of-repaglinide-and-its-protections-against-cyclosporine-a-induced-renal-tubular-injury
#9
Dao Li, Jin Li, Hui Li, Qiong Wu, Qi-Xiong Li
OBJECTIVES: Repaglinide (RG) is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus. It has a good safety and efficacy profile in diabetic patients with complications in renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal malfunctions. The aim of the present study was to examine the protective effect of RG on cyclosporine A (CsA)-induced rat renal impairment and to evaluate the antioxidant mechanisms by which RG exerts its protective actions...
July 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27631194/mapping-slco1b1-genetic-variation-for-global-precision-medicine-in-understudied-regions-in-africa-a-focus-on-zulu-and-cape-admixed-populations
#10
Nisreen Hoosain, Brendon Pearce, Clifford Jacobs, Mongi Benjeddou
The U.S. President Barack Obama has announced, in his State of the Union address on January 20, 2015, the Precision Medicine Initiative, a US$215-million program. For global precision medicine to become a reality, however, biological and environmental "variome" in previously understudied populations ought to be mapped and catalogued. Chief among the molecular targets that warrant global mapping is the organic anion-transporting polypeptide 1B1 (OATP1B1), encoded by solute carrier organic anion transporter family member 1B1 (SLCO1B1), a hepatic uptake transporter predominantly expressed in the basolateral side of hepatocytes...
September 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27599706/physiologically-based-pharmacokinetic-modeling-to-predict-drug-drug-interactions-with-efavirenz-involving-simultaneous-inducing-and-inhibitory-effects-on-cytochromes
#11
Catia Marzolini, Rajith Rajoli, Manuel Battegay, Luigia Elzi, David Back, Marco Siccardi
BACKGROUND: Antiretroviral drugs are among the therapeutic agents with the highest potential for drug-drug interactions (DDIs). In the absence of clinical data, DDIs are mainly predicted based on preclinical data and knowledge of the disposition of individual drugs. Predictions can be challenging, especially when antiretroviral drugs induce and inhibit multiple cytochrome P450 (CYP) isoenzymes simultaneously. METHODS: This study predicted the magnitude of the DDI between efavirenz, an inducer of CYP3A4 and inhibitor of CYP2C8, and dual CYP3A4/CYP2C8 substrates (repaglinide, montelukast, pioglitazone, paclitaxel) using a physiologically based pharmacokinetic (PBPK) modeling approach integrating concurrent effects on CYPs...
September 7, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27543206/transporter-expression-in-liver-tissue-from-subjects-with-alcoholic-or-hepatitis-c-cirrhosis-quantified-by-targeted-quantitative-proteomics
#12
Li Wang, Carol Collins, Edward J Kelly, Xiaoyan Chu, Adrian S Ray, Laurent Salphati, Guangqing Xiao, Caroline Lee, Yurong Lai, Mingxiang Liao, Anita Mathias, Raymond Evers, William Humphreys, Cornelis E C A Hop, Sean C Kumer, Jashvant D Unadkat
Although data are available on the change of expression/activity of drug-metabolizing enzymes in liver cirrhosis patients, corresponding data on transporter protein expression are not available. Therefore, using quantitative targeted proteomics, we compared our previous data on noncirrhotic control livers (n = 36) with the protein expression of major hepatobiliary transporters, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug and toxin extrusion protein 1 (MATE1), multidrug resistance-associated protein (MRP)2, MRP3, MRP4, sodium taurocholate-cotransporting polypeptide (NTCP), organic anion-transporting polypeptides (OATP)1B1, 1B3, 2B1, organic cation transporter 1 (OCT1), and P-glycoprotein (P-gp) in alcoholic (n = 27) and hepatitis C cirrhosis (n = 30) livers...
November 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27497002/c18-attached-membrane-funnel-based-spray-ionization-mass-spectrometry-for-quantification-of-anti-diabetic-drug-from-human-plasma
#13
Wan Li, Xiangfeng Chen, Y-L Elaine Wong, Y-L Winnie Hung, Ze Wang, Liulin Deng, T-W Dominic Chan
In this work, sorbent-attached membrane funnel-based spray ionization mass spectrometry was explored for quantitative analysis of anti-diabetic drugs spiked in human plasma. C18-attached membrane funnel was fabricated for in situ extraction and clean-up to alleviate matrix suppression effect in the ionization process. Repaglinide was used as a target analyte of anti-diabetic drugs. Under optimal working conditions, good linearity (R(2) > 0.99) was obtained in the concentration range of 1-100 ng mL(-1)...
August 24, 2016: Analytica Chimica Acta
https://www.readbyqxmd.com/read/27457785/clarification-of-the-mechanism-of-clopidogrel-mediated-drug-drug-interaction-in-a-clinical-cassette-small-dose-study-and-its-prediction-based-on-in-vitro-information
#14
Soo-Jin Kim, Takashi Yoshikado, Ichiro Ieiri, Kazuya Maeda, Miyuki Kimura, Shin Irie, Hiroyuki Kusuhara, Yuichi Sugiyama
Clopidogrel is reported to be associated with cerivastatin-induced rhabdomyolysis, and clopidogrel and its metabolites are capable of inhibiting CYP2C8 and OATP 1B1 in vitro. The objective of the present study was to identify the mechanism of clopidogrel-mediated drug-drug interactions (DDIs) on the pharmacokinetics of OATP1B1 and/or CYP2C8 substrates in vivo. A clinical cassette small-dose study using OATPs, CYP2C8, and OATP1B1/CYP2C8 probe drugs (pitavastatin, pioglitazone, and repaglinide, respectively) with or without the coadministration of either 600 mg rifampicin (an inhibitor for OATPs), 200 mg trimethoprim (an inhibitor for CYP2C8), or 300 mg clopidogrel was performed, and the area under the concentration-time curve (AUC) ratios (AUCRs) for probe substrates were predicted using a static model...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27435474/the-anti-diabetic-drug-repaglinide-induces-vasorelaxation-via-activation-of-pka-and-pkg-in-aortic-smooth-muscle
#15
Hye Won Kim, Hongliang Li, Han Sol Kim, Sung Eun Shin, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Amy L Firth, Hyoweon Bang, Won Sun Park
We investigated the vasorelaxant effect of repaglinide and its related signaling pathways using phenylephrine (Phe)-induced pre-contracted aortic rings. Repaglinide induced vasorelaxation in a concentration-dependent manner. The repaglinide-induced vasorelaxation was not affected by removal of the endothelium. In addition, application of a nitric oxide synthase inhibitor (L-NAME) and a small-conductance Ca(2+)-activated K(+) (SKCa) channel inhibitor (apamin) did not alter the vasorelaxant effect of repaglinide on endothelium-intact arteries...
September 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27404933/-a-rare-cause-of-diabetes-mellitus
#16
Chrysi Koliaki, Birgit Knebel, Fausto Machicao, Michael Roden, Karsten Müssig
UNLABELLED: Medical history and clinical examination: We report on a 52-year-old lean female patient with diabetes mellitus, treated with various glucose-lowering medications including insulin for 6 years. Both her mother and great-grandmother were also diagnosed with diabetes. At admission, she presents with good glycemic control and no signs of diabetes-related comorbidities. LABORATORY TESTS: HbA1c is 6 %. On the basis of positive family history for diabetes, normal body weight and negative antibodies against islet-cell antigens, we perform blood molecular genetic analyses with the suspicion of a genetic form of diabetes...
July 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27374668/effect-of-switching-from-sulphonylurea-to-repaglinide-twice-or-three-times-daily-for-4-months-on-glycemic-control-in-japanese-patients-with-type-2-diabetes
#17
Hiroshi Kamiyama, Kazutaka Aoki, Shigeru Nakajima, Kazuaki Shinoda, Kazunari Kamiko, Masataka Taguri, Yasuo Terauchi
Objective Switching from sulfonylureas to repaglinide in patients with type 2 diabetes improves glycemic control; however, the optimal dosage has not been fully evaluated. We designed to show that repaglinide was equivalent to sulfonylurea in Japanese patients with type 2 diabetes. We herein evaluated whether we could switch from sulfonylureas to repaglinide twice or thrice daily in Japanese adult patients who had been treated with anti-diabetic drugs, including sulfonylureas, and whose conditions were moderately well-controlled...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27305919/dissolution-rate-enhancement-of-repaglinide-using-dietary-fiber-as-a-promising-carrier
#18
Vivekanand K Chatap, Savita D Patil
In present investigation, an innovative attempt has been made to enhance the solubility and dissolution rate of Repaglinide (RPGD) using hydrothermally treated water insoluble dietary bamboo fibers (HVBF) as potential nutraceutical used in the treatment of diabetes mellitus. RPGD was selected as a model drug due to its low aqueous solubility and dissolution rate. Characterization of HVBF demonstrated the outstanding features like high surface area, maximum drug loading and increase dissolution rate and making HVBF as an excellent drug carrier...
2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27273149/pharmacokinetic-effects-of-isavuconazole-co-administration-with-the-cytochrome-p450-enzyme-substrates-bupropion-repaglinide-caffeine-dextromethorphan-and-methadone-in-healthy-subjects
#19
Takao Yamazaki, Amit Desai, Ronald Goldwater, David Han, Corrie Howieson, Shahzad Akhtar, Donna Kowalski, Christopher Lademacher, Helene Pearlman, Diane Rammelsberg, Robert Townsend
This report describes phase I clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg [administered as isavuconazonium sulfate 372 mg] three times a day for 2 days; 200 mg once daily thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23)...
June 8, 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27259818/cyp2c8-mediated-interaction-between-repaglinide-and-steviol-acyl-glucuronide-in%C3%A2-vitro-investigations-using-rat-and-human-matrices-and-in%C3%A2-vivo-pharmacokinetic-evaluation-in-rats
#20
Yunting Xu, Dandan Zhou, Yedong Wang, Jiajun Li, Meiyu Wang, Jia Lu, Hongjian Zhang
CYP2C8 is involved in the metabolic clearance of several important drugs and recent reports have shown that acyl glucuronides of gemfibrozil and clopidogrel are potent time-dependent inhibitors of CYP2C8 activity. In the present study, the inhibitory effect of steviol acyl glucuronide (SVAG), a circulating metabolite formed after the ingestion of rebaudioside A, was investigated using in vitro and in vivo systems. Results indicated that SVAG was a reversible but not a time-dependent inhibitor of CYP2C8-mediated paclitaxel 6α-hydroxylation...
August 2016: Food and Chemical Toxicology
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