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Repaglinide

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https://www.readbyqxmd.com/read/29199116/repaglinide-versus-insulin-for-newly-diagnosed-diabetes-in-patients-with-cystic-fibrosis-a-multicentre-open-label-randomised-trial
#1
Manfred Ballmann, Dominique Hubert, Baroukh M Assael, Doris Staab, Alexandra Hebestreit, Lutz Naehrlich, Tanja Nickolay, Nicole Prinz, Reinhard W Holl
BACKGROUND: As survival among patients with cystic fibrosis has improved in recent decades, complications have become increasingly relevant. The most frequent complication is cystic-fibrosis-related diabetes. The recommended treatment is injected insulin, but some patients are treated with oral antidiabetic drugs to ease the treatment burden. We assessed the efficacy and safety of oral antidiabetic drugs. METHODS: We did a multicentre, open-label, comparative, randomised trial in 49 centres in Austria, France, Germany, and Italy...
November 30, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29108130/comparative-risk-of-serious-hypoglycemia-with-oral-antidiabetic-monotherapy-a-retrospective-cohort-study
#2
Charles E Leonard, Xu Han, Colleen M Brensinger, Warren B Bilker, Serena Cardillo, James H Flory, Sean Hennessy
PURPOSE: To examine and compare risks of serious hypoglycemia among antidiabetic monotherapy-treated adults receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione. METHODS: We performed a retrospective cohort study of apparently new users of monotherapy with metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide within a dataset of Medicaid beneficiaries from California, Florida, New York, Ohio, and Pennsylvania...
November 6, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29069819/comparison-of-twelve-single-drug-regimens-for-the-treatment-of-type-2-diabetes-mellitus
#3
Shao-Lian Wang, Wen-Bin Dong, Xiao-Lin Dong, Wen-Min Zhu, Fang-Fang Wang, Fang Han, Xin Yan
We performed a network meta-analysis to compare the efficacy of 12 single-drug regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide, Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant randomized controlled trials (RCTs) were included; direct and indirect evidence from these studies was combined, and weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRAs) were examined to evaluate the monotherapies...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058840/-use-of-oral-glucose-lowering-agents-in-patients-with-renal-impairment
#4
A J Scheen, N Paquot
Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are increasingly numerous, especially in the elderly population. Surprisingly, this situation is often under-recognized or even neglected in clinical practice. Yet, most oral antidiabetic (OAD) agents have limitations in case of renal impairment, either because they require a dose reduction, or are contra-indicated mainly for safety reasons. This clinical case gives the opportunity to discuss the modalities of prescription and cautions to be taken when using most commonly prescribed OAD, metformin, insulin secretagogues (sulfonylureas, repaglinide), DPP-4 inhibitors (gliptins) and SGLT2 inhibitors, in a patient with T2D and CKD...
October 2017: Revue Médicale de Liège
https://www.readbyqxmd.com/read/29038231/evaluation-of-clinical-drug-interaction-potential-of-clofazimine-using-static-and-dynamic-modeling-approaches
#5
Ramachandra Sangana, Helen Gu, Dung Yu Chun, Heidi J Einolf
The 2016 World Health Organization treatment recommendations for drug-resistant tuberculosis (DR-TB) positioned clofazimine as a core second-line drug. Being identified as a cytochrome P450 (CYP) inhibitor in vitro, a CYP-mediated drug interaction may be likely when clofazimine is co-administered with substrates of these enzymes. The CYP-mediated drug interaction potential of clofazimine was evaluated using both static (estimation of "R1" and area under the plasma concentration-time curve ratio [AUCR] values) and dynamic (physiologically based pharmacokinetic [PBPK]) modeling approaches...
October 16, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29021480/the-effects-of-mitiglinide-and-repaglinide-on-postprandial-hyperglycemia-in-patients-undergoing-methylprednisolone-pulse-therapy
#6
Kenichi Tanaka, Yosuke Okada, Hiroko Mori, Keiichi Torimoto, Tadashi Arao, Yoshiya Tanaka
One adverse effect of methylprednisolone (MP) pulse therapy is an acute dose-dependent increase in the blood glucose level. Five patients with thyroid ophthalmopathy but normal glucose tolerance received MP pulse therapy (3 cycles, 3 days/week) and were assessed by continuous glucose monitoring. Steroid therapy increased the mean sensor glucose level, and all patients developed steroid-induced diabetes. The patients were treated alternately with mitiglinide (30 mg/day) and repaglinide (1.5 mg/day) during the second or third MP pulse therapy...
October 11, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28977924/antihyperglycemic-treatment-in-patients-with-type-2-diabetes-in-italy-the-impact-of-age-and-kidney-function
#7
Sandro Gentile, Pamela Piscitelli, Francesca Viazzi, Giuseppina Russo, Antonio Ceriello, Carlo Giorda, Piero Guida, Paola Fioretto, Roberto Pontremoli, Felice Strollo, Salvatore De Cosmo
We describe AHA utilization pattern according to age and renal function in type 2 diabetes mellitus (T2DM), in real-life conditions. The analysis was performed using the data set of electronic medical records collected between 1 January and 31 December, 2011 in 207 Italian diabetes centers. The study population consisted of 157,595 individuals with T2DM. The AHA treatment regimens was evaluated. Kidney function was assessed by eGFR, estimated using the CKD-EPI formula. Other determinations: HbA1c, blood pressure (BP), low- density lipoprotein (LDL-c), total and high density lipoprotein cholesterol (TC and HDL-c), triglycerides (TG) and serum uric acid (SUA)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28891561/online-monitoring-of-hepatic-rat-metabolism-by-coupling-a-liver-biochip-and-a-mass-spectrometer
#8
Franck Merlier, Rachid Jellali, Eric Leclerc
A microfluidic liver biochip was coupled with a mass spectrometer to detect in real time the drug metabolism of hepatocytes. The hepatocytes were cultivated in the biochip for 35 h. The biochip was placed in a small-scale incubator in which the temperature and CO2 concentration were controlled. The biochip was connected serially to a mass spectrometer, a peristaltic pump and a culture medium reservoir. The injection in the mass spectrometer was performed every 10 min for 11 h. The metabolism of midazolam, phenacetin, omeprazole, dextromethorphan, repaglinide, rosuvastatin, tolbutamide and caffeine was investigated...
September 25, 2017: Analyst
https://www.readbyqxmd.com/read/28811859/long-term-effect-of-alogliptin-on-glycemic-control-in-japanese-patients-with-type-2-diabetes-a-3-5-year-observational-study
#9
Kohzo Takebayashi, Tatsuhiko Suzuki, Rika Naruse, Kenji Hara, Mariko Suetsugu, Takafumi Tsuchiya, Toshihiko Inukai
BACKGROUND: The goal of the current study was to investigate the long-term effects (after 3 years or more) of alogliptin on glycemic control in Japanese patients with type 2 diabetes. METHODS: We retrospectively studied the effect of alogliptin on glycemic control in the patients with type 2 diabetes who had participated in our previous 3-month study and who continued to take alogliptin for at least 36 months. RESULTS: The mean duration of alogliptin treatment was 42...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28717973/design-and-development-of-repaglinide-microemulsion-gel-for-transdermal-delivery
#10
Ujwala A Shinde, Sheela H Modani, Kavita H Singh
Microemulsion formulation of repaglinide, a BCS class II hypoglycemic agent with limited oral bioavailability, was developed considering its solubility in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagrams for microemulsion regions were constructed by water titration method at K m 1:1 and characterized for optical birefringence, percentage transmittance, pH, refractive index, globule size, zeta potential, viscosity, drug content, and thermodynamic stability. To enhance the drug permeation and residence time, the optimized microemulsions having mean globule size of 36...
July 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28700358/antihyperglycemic-treatment-in-patients-with-type-2-diabetes-in-italy-the-impact-of-age-and-kidney-function
#11
Sandro Gentile, Pamela Piscitelli, Francesca Viazzi, Giuseppina Russo, Antonio Ceriello, Carlo Giorda, Piero Guida, Paola Fioretto, Roberto Pontremoli, Felice Strollo, Salvatore De Cosmo, The Amd-Annals Study Group
We describe AHA utilization pattern according to age and renal function in type 2 diabetes mellitus (T2DM), in real-life conditions.The analysis was performed using the data set of electronic medical records collected between 1 January and 31 December, 2011 in 207 Italian diabetes centers. The study population consisted of 157,595 individuals with T2DM. The AHA treatment regimens was evaluated. Kidney function was assessed by eGFR, estimated using the CKD-EPI formula. Other determinations: HbA1c, blood pressure (BP), low- density lipoprotein (LDL-c), total and high density lipoprotein cholesterol (TC and HDL-c), triglycerides (TG) and serum uric acid (SUA)...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28653847/glucuronides-as-potential-anionic-substrates-of-human-cytochrome-p450-2c8-cyp2c8
#12
Yong Ma, Yue Fu, S Cyrus Khojasteh, Deepak Dalvie, Donglu Zhang
Glucuronidation is in general considered as a terminal metabolic step that leads to direct elimination of drugs and generally abolishes their biological activity. However, there is growing evidence to suggest that glucuronides can be ligands of human CYP2C8, making CYP2C8 distinct from the other CYP isoforms. Several classes of glucuronide conjugates, which include acyl glucuronides, ether glucuronides, N-glucuronides, and carbamoyl glucuronides, have been shown to be substrates or time-dependent inhibitors of CYP2C8...
June 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28653144/explaining-ethnic-variability-of-transporter-substrate-pharmacokinetics-in-healthy-asian-and-caucasian-subjects-with-allele-frequencies-of-oatp1b1-and-bcrp-a-mechanistic-modeling-analysis
#13
Rui Li, Hugh A Barton
BACKGROUND: Ethnic variability in the pharmacokinetics of organic anion transporting polypeptide (OATP) 1B1 substrates has been observed, but its basis is unclear. A previous study hypothesizes that, without applying an intrinsic ethnic variability in transporter activity, allele frequencies of transporters cannot explain observed ethnic variability in pharmacokinetics. However, this hypothesis contradicts the data collected from compounds that are OATP1B1 substrates but not breast cancer resistance protein (BCRP) substrates...
June 26, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28617932/effect-of-the-treatment-of-type-2-diabetes-mellitus-on-the-development-of-cognitive-impairment-and-dementia
#14
REVIEW
Almudena Areosa Sastre, Robin Wm Vernooij, Magali González-Colaço Harmand, Gabriel Martínez
BACKGROUND: Prevention of cognitive impairment and dementia is an important public health goal. Epidemiological evidence shows a relationship between cognitive impairment and Type 2 diabetes mellitus. The risk of dementia increases with duration of disease. This updated systematic review investigated the effect on cognitive function of the type of treatment and level of metabolic control in people with Type 2 diabetes. OBJECTIVES: To assess the effects of different strategies for managing Type 2 diabetes mellitus on cognitive function and the incidence of dementia...
June 15, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28574832/impact-of-chronic-unpredicted-mild-stress-induced-depression-on-repaglinide-fate-via-glucocorticoid-signaling-pathway
#15
Hongyan Wei, Ting Zhou, Boyu Tan, Lei Zhang, Mingming Li, Zhijun Xiao, Feng Xu
Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28495568/quantitative-analyses-of-the-influence-of-parameters-governing-rate-determining-process-of-hepatic-elimination-of-drugs-on-the-magnitudes-of-drug-drug-interactions-via-hepatic-oatps-and-cyp3a-using-physiologically-based-pharmacokinetic-models
#16
Takashi Yoshikado, Kazuya Maeda, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
Physiologically based pharmacokinetic models were constructed for hepatic organic anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) substrates (bosentan, repaglinide, clarithromycin, and simeprevir), a CYP3A probe substrate (midazolam), and selective inhibitors for OATPs (rifampicin) and CYP3A (itraconazole), although the role of OATPs in the hepatic uptake of clarithromycin is unclear. The pharmacokinetic data were obtained from our previous clinical drug-drug interaction (DDI) study. Parameters optimized from clinical PK data were confirmed to reproduce their blood concentrations in control phase...
May 8, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28484975/a-clinical-cassette-dosing-study-for-evaluating-the-contribution-of-hepatic-oatps-and-cyp3a-to-drug-drug-interactions
#17
Takashi Yoshikado, Kazuya Maeda, Sawako Furihata, Hanano Terashima, Takeshi Nakayama, Keiko Ishigame, Kazunobu Tsunemoto, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
PURPOSE: To demonstrate the relative importance of organic anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) in the hepatic elimination of substrate drugs. METHODS: A cocktail of subtherapeutic doses of bosentan, repaglinide, clarithromycin, darunavir, simeprevir, and midazolam (CYP3A probe) was administered orally to eight healthy volunteers. Rifampicin (OATP inhibitor; 600 mg, p.o.) and itraconazole (CYP3A inhibitor; 200 mg, i.v.) were coadministered with the cocktail in the second and third phases, respectively...
August 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28483598/the-mechano-sensitivity-of-cardiac-atp-sensitive-potassium-channels-is-mediated-by-intrinsic-mgatpase-activity
#18
Mohammad Fatehi, Christian C Carter, Nermeen Youssef, Peter E Light
Cardiac ATP-sensitive K(+) (KATP) channel activity plays an important cardio-protective role in regulating excitability in response to metabolic stress. Evidence suggests that these channels are also mechano-sensitive and therefore may couple KATP channel activity to increased cardiac workloads. However, the molecular mechanism that couples membrane stretch to channel activity is not currently known. We hypothesized that membrane stretch may alter the intrinsic MgATPase activity of the cardiac KATP channel resulting in increased channel activation...
May 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28479356/quantitative-analysis-of-complex-drug-drug-interactions-between-repaglinide-and-cyclosporin-a-gemfibrozil-using-physiologically-based-pharmacokinetic-models-with-in%C3%A2-vitro-transporter-enzyme-inhibition-data
#19
Soo-Jin Kim, Kota Toshimoto, Yoshiaki Yao, Takashi Yoshikado, Yuichi Sugiyama
Quantitative analysis of transporter- and enzyme-mediated complex drug-drug interactions (DDIs) is challenging. Repaglinide (RPG) is transported into the liver by OATP1B1 and then is metabolized by CYP2C8 and CYP3A4. The purpose of this study was to describe the complex DDIs of RPG quantitatively based on unified physiologically based pharmacokinetic (PBPK) models using in vitro Ki values for OATP1B1, CYP3A4, and CYP2C8. Cyclosporin A (CsA) or gemfibrozil (GEM) increased the blood concentrations of RPG. The time profiles of RPG and the inhibitors were analyzed by PBPK models, considering the inhibition of OATP1B1 and CYP3A4 by CsA or OATP1B1 inhibition by GEM and its glucuronide and the mechanism-based inhibition of CYP2C8 by GEM glucuronide...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28476618/identification-of-repaglinide-as-a-therapeutic-drug-for-glioblastoma-multiforme
#20
Zui Xuan Xiao, Ruo Qiao Chen, Dian Xing Hu, Xiao Qiang Xie, Shang Bin Yu, Xiao Qian Chen
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a median survival time of only 14 months after treatment. It is urgent to find new therapeutic drugs that increase survival time of GBM patients. To achieve this goal, we screened differentially expressed genes between long-term and short-term survived GBM patients from Gene Expression Omnibus database and found gene expression signature for the long-term survived GBM patients. The signaling networks of all those differentially expressed genes converged to protein binding, extracellular matrix and tissue development as revealed in BiNGO and Cytoscape...
June 17, 2017: Biochemical and Biophysical Research Communications
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