Abstract:
PURPOSE:Breast cancer resistance protein (BCRP/ABCG2) is a drug efflux transporter expressed at the blood cerebrospinal fluid barrier (BCSFB), and influences distribution of drugs into the central nervous systems (CNS). Current inhibitors have failed clinically due to neurotoxicity. Novel approaches are needed to identify new modulators to enhance CNS delivery. This study examines 18 compounds (mainly phytoestrogens) as modulators of the expression/function of BCRP in an in vitro rat choroid plexus BCSFB model. METHODS:Modulators were initially subject to cytotoxicity (MTT) assessment to determine optimal non-toxic concentrations. Reverse-transcriptase PCR and confocal microscopy were used to identify the presence of BCRP in Z310 cells. Thereafter modulation of the intracellular accumulation of the fluorescent BCRP probe substrate Hoechst 33342 (H33342), changes in protein expression of BCRP (western blotting) and the functional activity of BCRP (membrane insert model) were assessed under modulator exposure. RESULTS:A 24 hour cytotoxicity assay (0.001 µM-1000 µM) demonstrated the majority of modulators possessed a cellular viability IC50 > 148 µM. Intracellular accumulation of H33342 was significantly increased in the presence of the known BCRP inhibitor Ko143 and, following a 24 hour pre-incubation, all modulators demonstrated statistically significant increases in H33342 accumulation (P < 0.001), when compared to control and Ko143. After a 24 hour pre-incubation with modulators alone, a 0.16-2.5 -fold change in BCRP expression was observed for test compounds. The functional consequences of this were confirmed in a permeable insert model of the BCSFB which demonstrated that 17-β-estradiol, naringin and silymarin (down-regulators) and baicalin (up-regulator) can modulate BCRP-mediated transport function at the BCSFB. CONCLUSION:We have successfully confirmed the gene and protein expression of BCRP in Z310 cells and demonstrated the potential for phytoestrogen modulators to influence the functionality of BCRP at the BCSFB and thereby potentially allowing manipulation of CNS drug disposition.
journal_name
J Pharm Pharm Sciauthors
Kaur M,Badhan RKdoi
10.18433/j3p31ksubject
Has Abstractpub_date
2015-01-01 00:00:00pages
132-54issue
2issn
1482-1826journal_volume
18pub_type
杂志文章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
abstract:PURPOSE:To investigate the suitability of an SCMC (sodium carboxymethyl cellulose/polyethylene glycol 400/carbopol 934P) and an HPMC (hydroxypropylmethyl cellulose/polyethylene glycol 400/carbopol 934P) films as drug vehicle for buccal delivery. METHODS:The mechanical and in vitro bioadhesive strength properties of th...
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:1999-05-01 00:00:00
abstract:PURPOSE:To investigate the effect of clofibrate on inducing liver fatty acid binding protein (FABP1) following a high-fat load in a hepatocyte cell culture model. METHODS:Rat hepatoma cells (CRL-1548) were treated with a fatty acid (FA) mixture consisting of oleate:palmitate (2:1) in the presence of 3% albumin. Cells ...
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/J3TS70
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:Autism, a neuropsychiatric illness, is a complex ailment of mainly indefinite cause. Although precise pathophysiological mechanism is unclear but the role of genetics is undeniable therefore pharmacogenetics may assist to a better management of symptoms. Risperidone is widely used in autism. Considering the sig...
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/J3H63T
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:Tramadol Hydrochloride is a widely-used centrally acting analgesic drug, which has some features of being a P-gp substrate. The present study evaluates the functional involvement of P-gp in CNS distribution of tramadol. METHODS:The possible involvement of P-glycoprotein in brain distribution of tramadol was ev...
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/j3d60r
更新日期:2012-01-01 00:00:00
abstract::In noncompartmental analysis, poor characterization of the terminal elimination rate constant (Kel) will lead to biased results for half-life and total exposure (AUCinf), providing incorrect relative bioavailability and bioequivalence conclusions. We set out to determine if the sampling scheme duration was crucial for...
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/j3fg63
更新日期:2011-01-01 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:The gastrointestinal damage induced by xenobiotics is occurring more frequently and with greater toxicological significance than previously thought. Although there are some preliminary clinical studies and reports, there does not appear to be an extensive examination of gastrointestinal toxicity of various chem...
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::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
abstract:PURPOSE:The aim of this study was to correlate the relationship between the pharmacokinetic behaviors and the toxicity of a new investigational anticancer agent CZ48, a C20-propionate ester of camptothecin (CPT) in mice. METHODS:In this study, the safety and pharmacokinetics of oral doses of CZ48 were compared with th...
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/j3b604
更新日期:2013-01-01 00:00:00
abstract:PURPOSE:The purpose of this study was the use of animal models to demonstrate the importance of drug delivery (verteporfin) to plasma lipoproteins in order to attain efficacy of photodynamic therapy (PDT) in vivo. METHODS:Photosensitizers appropriately formulated in various vehicles such as pluronics and lipid-based s...
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:2003-05-01 00:00:00
abstract:PURPOSE:Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. METHODS:Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different o...
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,多中心研究,随机对照试验
doi:10.18433/j3388p
更新日期:2010-01-01 00:00:00
abstract::Hypochlorhydria is a condition where the production of hydrochloric acid in the stomach is decreased. As a result, the intragastric pH is elevated. This condition can be due to a series of causes, such as disease (gastric mucosal infection caused by Helicobacter pylori and is prominent in AIDS patients), ethnicity, ag...
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/jpps30227
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:This work describes the preparation of new nanocomposites based on lamellar silicates (AAM-alkyl ammonium montmorillonite) obtained by the intercalation of PVP K30 and glyceril monostearate. METHODS:By XRD, TGA and DSC analysis the AAM was characterized and its compactation characteristics, functionality and t...
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/j3hc72
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:Patients with type 2 diabetes are generally treated with various pharmacological compounds and are exposed to a high risk of drug-drug interactions. However, alterations of pharmacokinetics in a type 2 diabetes model have been obscure. The present study was undertaken to investigate the effects of type 2 diabet...
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/j3mc70
更新日期:2014-01-01 00:00:00
abstract:PURPOSE:A few studies have shown that normothermic hepatic ischemia-reperfusion (IR) injury may affect the mRNA and/or protein levels of canalicular transporters P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2). However, the effects of the injury on the functions of these canalicular transport...
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: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:PURPOSE:Monoclonal antibodies (mAbs) are commonly administered by subcutaneous (SC) route. However, bioavailability is often reduced after SC administration. In addition, the sequential transfer of mAbs through the SC tissue and lymphatic system is not completely understood. Therefore, major objectives of this study we...
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/jpps30028
更新日期:2018-01-01 00:00:00
abstract:PURPOSE:The adrenoceptor family, as one of the main contributors in regulating the noradrenergic system, has been studied in involvement of depression and its treatment. A functional polymorphism of G1165C on beta adrenoceptor (βAR) enhances post receptor signalling and is assumed to be involved in pharmacotherapy of d...
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
abstract::Purpose - The CEIBA cocktail consisting of caffeine (CAF), omeprazole (OZ), dextromethorphan (DM) and losartan (LOS) was previously proposed for the clinical phenotyping of five major human cytochrome P450 (CYP) isoenzymes. This work aimed to assess the usefulness of CEIBA cocktail to study non-clinical drug interacti...
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/J3D313
更新日期:2016-01-01 00:00:00
abstract::This review discusses issues largely from the biological point of view about the targeted approaches for the use of natural products for the discovery of anti-diabetic drugs in collaboration with medicinal chemists and computer-aided drug design. A major thrust of this review reflects the collaborative research of fou...
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/j3t60g
更新日期:2013-01-01 00:00:00
abstract:PURPOSE:The purpose of this work was to investigate the potential effectiveness of polaprezinc in the treatment of stomatitis. Its effect on oral mucous membrane lesions was studied focusing on acetic acid-induced stomatitis in an animal model. METHOD:Stomatitis was induced in hamsters by local injection of 30 microL ...
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:2000-01-01 00:00:00
abstract::Cannabis has been used for its medicinal purposes since ancient times. Its consumption leads to the activation of Cannabis receptors CB1 and CB2 that, through specific mechanisms can lead to modulation and progression of inflammation or repair. The novel findings are linked to the medical use of Cannabis in gastrointe...
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/jpps31242
更新日期:2020-01-01 00:00:00
abstract:PURPOSE:The primary aim of this work was to establish a radiolabeling procedure of vinblastine, a vinca alkaloid widely used in chemotherapy, with the positron-emitter carbon-11 for application in positron-emission-tomography (PET) studies in cancer patients. The optimized reaction conditions were transferred to an aut...
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: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 ...
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/j3m89q
更新日期:2014-01-01 00:00:00
abstract:PURPOSE:The aim of the study is to evaluate the effect of different acidic compounds on the inclusion of miconazole (MICO) in several cyclodextrins (CDs) using supercritical carbon dioxide (SCCO(2) ) processing. METHODS:Physical mixtures were processed by SCCO(2) at 30 MPa, 125 degrees C during 60 minutes in a static ...
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:2004-11-30 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: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
abstract:PURPOSE:The extent of palmitate uptake by hepatocytes is dependent upon the surface charge of the extracellular binding protein. Specifically, hepatocyte uptake is greater when palmitate is bound to cationic binding proteins than when it is bound to anionic proteins. To further understand the role of protein surface ch...
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/j3bc8w
更新日期:2012-01-01 00:00:00
abstract:PURPOSE:To assess the predicted rate and the factors associated with bleeding events among patients with non-valvular atrial fibrillation (NVAF) receiving dabigatran therapy. METHODS:This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified ...
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/J3TP9Q
更新日期:2017-01-01 00:00:00