Abstract:
PURPOSE:Organic anion-transporting polypeptide (OATP) 1B1 and OATP1B3 contribute to hepatic uptake of numerous drugs. Thus, reduced OATP1B1 and OATP1B3 activity in chronic kidney disease (CKD) may have a major impact on the hepatic clearance of drugs. The effect of drug-uremic toxin interactions on OATP1B1 and OATP1B3 has not been well studied. In the present study, we examine the inhibitory effects of uremic toxins on OATP1B1 and OATP1B3 transport activity to evaluate the interactions between drugs and uremic toxins in patients with chronic kidney disease. METHODS. [3H]Estron-3-sulfate, [3H]taurocholate uptake and [3H]methotrexate by OATP1B1 and OATP1B3 expressing HEK293 cells were performed to evaluate the inhibitory effect of uremic toxins. To clarify whether the uremic toxins that interact with OATP1B1 and/or OATP1B3 were substrates for these transporters, we performed uptake studies. RESULTS. Four uremic toxins, kynurenic acid, indole-3-acetic acid, indoxyl sulfate, and p-cresol, inhibited OATP1B1- and OATP1B3-mediated transport in a concentration-dependent manner, with IC50 values of 180, 770, 2700, and 4600 µM, respectively, for OATP1B1 and 180, 1100, 1300, and 1700 µM, respectively, for OATP1B3. [3H]Methotrexate uptake by OATPs was also inhibited by the four uremic toxins in a dose-dependent manner. Uptake studies revealed that kynurenic acid is a substrate for both the OATP1B1 and OATP1B3. Moreover, OATP1B3 was involved in the transport of indoxyl sulfate. Indole-3-acetic acid and p-cresol were not significantly transported by OATP1B1 and OATP1B3. CONCLUSIONS. We showed that some uremic toxins inhibit OATP-mediated uptake in a concentration-dependent manner, and clarified OATPs contribution to uremic toxin handling in the liver. Thus, we provided basic information to estimate the inhibitory effects of uremic toxins on OATPs in CKD patients. These data suggest that the dose of drugs excreted via renal and non-renal pathways should be carefully adjusted in CKD patients.
journal_name
J Pharm Pharm Sciauthors
Sato T,Yamaguchi H,Kogawa T,Abe T,Mano Ndoi
10.18433/j3m89qsubject
Has Abstractpub_date
2014-01-01 00:00:00pages
475-84issue
4issn
1482-1826journal_volume
17pub_type
杂志文章abstract:PURPOSE:The purpose of our study was to optimize lipid-lowering therapy in patients undergoing coronary revascularization and to determine whether the percentage change in low-density lipoprotein-cholesterol (LDL-C) level in the 3 months after coronary revascularization could be used as a predictor of the time to recur...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3hg6q
更新日期:2010-01-01 00:00:00
abstract:PURPOSE:To evaluate the metabolism of amiodarone (AM) to desethylamiodarone (DEA) by selected human and rat cytochrome P450, and the inhibitory effect of ketoconazole (KTZ). METHODS:Some important CYP isoenzymes (rat CYP1A1, 1A2, 2C6, 2C11, 2D1, 2D2, and 3A1 and human CYP1A1, 1A2, 2D6 and 3A4) were spiked with various...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3sg66
更新日期:2008-01-01 00:00:00
abstract:INTRODUCTION:Inhalation anesthetics have been shown to have electrical suppressant effects on excitable membranes such as the cardiac conduction system. Therefore, the anesthetized patient or laboratory animal may respond differently to cardiac drugs when compared with their conscious counterparts. The purpose of this ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract:BACKGROUND:The identification of fragment sequences, or motifs, within a therapeutic protein that may elicit an immune response when processed by T-cells can be provided by computer-aided approaches. Immunogenicity is a significant problem associated with protein therapeutics and should be investigated in the early sta...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/jpps29800
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:Status epilepticus (SE) is characterized by recurrent seizure activity and can be drug- resistant. Knowledge of neuronal and metabolic activity of the brain during SE may be helpful to improve medical care. We here report the effects of three anti-seizure drugs on changes of acetylcholine energy metabolites and...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/jpps30439
更新日期:2019-01-01 00:00:00
abstract:PURPOSE:Regular exercise training and metformin medication are widely considered to increase insulin sensitivity and protect against type 2 diabetes, however, evaluating the effect of exercise training on the disposition and pharmacokinetics of metformin is unclear. METHODS:We investigated the effect of a 4-wk swim tr...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3tg7w
更新日期:2012-01-01 00:00:00
abstract::Years after the first report on 1,4-dihydropyridines (1,4-DHPs) and 1,2,3,4-tetrahydropyrimidines (1,2,3,4-THPMs) appeared, they are revisited as plausible therapeutic agents. This is mainly due to the convenient methods that exist for their synthesis and the diverse pharmacologic properties that these scaffolds prese...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,评审
doi:10.18433/j3q01v
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:The purpose of this review article is to review the development of a number of liposomal polyene antibiotics. BACKGROUND:In the past thirty years, the increase in life-threatening pre-systemic and systemic fungal infections within cancer, diabetic and AIDS patients have reached alarming proportions. A number o...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 历史文章,杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
abstract::Life-threatening fungal infections have increased dramatically in recent decades in immunocompromised patients. An estimated 40% of all deaths from hospital-acquired infections are due to infections caused by opportunistic fungi. The current treatment options are either causing serious toxicity, or becoming inactive a...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3h010
更新日期:2008-07-06 00:00:00
abstract:PURPOSE:To provide predictive cosolvency models, the Abraham solvation parameters of solutes and the solvent coefficients were combined with the Jouyban-Acree and the log-linear models. These models require two and one solubility data points to predict the solubility of drugs in water-cosolvent mixtures. Ab initio pred...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:To assess the stability of sulfadiazine (SDZ) oral liquids prepared from tablets and powder at two temperatures. METHODS:Solutions of SDZ 200 mg/mL were prepared from commercially available 500 mg tablets and powder in sterile water for irrigation. They were stored in amber glass bottles at 4 degrees C and 23 ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2004-04-21 00:00:00
abstract:PURPOSE:To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers. METHODS:An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 临床试验,杂志文章
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更新日期:2016-04-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2004-09-24 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract:PURPOSE:An improved HPLC method with fluorescence detection was developed and validated for determination of glucosamine in human and rat biological samples. METHOD:Aliquot of 0.1 mL plasma was spiked with mannosamine HCl as the internal standard (IS); proteins were precipitated with acetonitrile; the clear layer was ...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3t01s
更新日期:2010-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2005-08-03 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
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更新日期:2012-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
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更新日期:2017-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/J3W31F
更新日期:2017-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,评审
doi:10.18433/j3jc7c
更新日期:2010-01-01 00:00:00
abstract:PURPOSE:To develop an HPLC method using fluorescence detection for the pharmacokinetic evaluation of levels of zabofloxacin, a novel broad spectrum fluoroquinolone antibiotic, in the plasma, bile and urine of rats. METHODS:A simple reversed-phase HPLC method using a C18 column with fluorescence detection was developed...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3j592
更新日期:2011-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j30593
更新日期:2007-01-01 00:00:00
abstract::Cardiac ischemia-reperfusion stimulates the renin-angiotensin system (RAS) associated with elevated levels of circulating angiotensin II. Numerous studies demonstrate that the antagonist for the angiotensin II type 1 receptor, losartan improves cardiac function in animal models of ischemia-reperfusion. Molecular mecha...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章,评审
doi:10.18433/j3nw2k
更新日期:2015-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
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journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3ms40
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:To evaluate the inhibitory activity of active compounds isolated from Cinnamomum cassia bark against lens aldose reductase and compare to that of three commercially available compounds (cinnamyl alcohol, trans -cinnamic acid, and eugenol) and quercitrin as aldose reductase inhibitors. The IC (50) value of cinna...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract:PURPOSE:To study the influence of inspiratory flow rate on the fine particle mass and the particle size distribution for metered dose inhaler (MDI) and dry powder inhaler (DPI) glucocorticoid products, in vitro. To compare the performance of MDI and DPI inhalers containing the same drug and strength at an impaction flo...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:PURPOSE:Because oxytocin (OT) is potentially useful in cardiovascular therapy but has hormonal roles on the cardiovascular and renal systems, we characterized its pharmacokinetic (PK) properties as a function of dose. METHODS:A single intravenous bolus of OT was given at doses of 200, 300, 500, 1000, 3000, 5000 and 10...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j3pk5x
更新日期:2008-01-01 00:00:00
abstract:PURPOSE:The purpose of this study was to develop an artificial neural network (ANN) model to predict drug removal during dialysis based on drug properties and dialysis conditions. Nine antihypertensive drugs were chosen as model for this study. METHODS:Drugs were dissolved in a physiologic buffer and dialysed in vitro...
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j35c8b
更新日期:2013-01-01 00:00:00
abstract::P-glycoprotein (Pgp), a protein codified by Multi Drug Resistance (MDR1) gene, has a detoxifying function and might influence the toxicity and pharmacokinetics and pharmacodynamics of drugs. Sampling strategies to improve Pgp studies could be useful to optimize the sensitivity and the reproducibility of efflux assays....
journal_title:Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
pub_type: 杂志文章
doi:10.18433/j34g69
更新日期:2009-01-01 00:00:00