MDR1 haplotypes significantly minimize intracellular uptake and transcellular P-gp substrate transport in recombinant LLC-PK1 cells.


:To date, research on the effect of single nucleotide polymorphisms (SNPs) on P-glycoprotein (P-gp) expression and functionality has rendered inconsistent results. This study systematically evaluates the impact of MDR1 haplotypes (1236/2677, 1236/3435, 2677/3435, 1236/2677/3435) on P-gp functionality compared to individual SNPs (1236, 2677, and 3435) in validated stable recombinant epithelial cells. Recombinant LLC-PK1 cells expressing MDR1wt or its variants were developed and validated for this purpose. Intracellular accumulation and time-dependant efflux of a P-gp substrate, Rhodamine 123 (R123, 5 microM) were evaluated in control and recombinant cells. Additionally, the transepithelial transport of R123 (1 microM) and Vinca alkaloids (5 microM) was evaluated. Except for MDR1(2677T) and MDR1(1236T/2677T/3435T), cells expressing MDR1 variants displayed intermediate R123 intracellular accumulation (1.5-2-fold higher) and lower effluxed R123 (10-20% vs. 52%) compared to those expressing MDR1wt. Efflux ratios across MDR1wt expressing cells were significantly larger for R123 (3.95+/-1.1), Vinblastine (3.75+/-0.26), and Vincristine (2.8+/-0.29). Recombinant cells expressing MDR1 variants displayed 0%-22.7% P-gp activity (approximately 80%-100% efflux loss). Results suggest that MDR1 polymorphisms at the 1236, 2677, and/or 3435 positions significantly minimize P-gp functionality in vitro, the extent of which appears to be substrate dependant.


J Pharm Sci


Salama NN,Yang Z,Bui T,Ho RJ




Has Abstract


2006-10-01 00:00:00














  • Usefulness of a novel Caco-2 cell perfusion system. I. In vitro prediction of the absorption potential of passively diffused compounds.

    abstract::A simple, reliable, and user friendly system was established to cultivate Caco-2 cell monolayer for epithelial transport studies. After an initial growth period of 1 week in a CO(2) incubator, Caco-2 cells were cultivated in an automated continuous perfusion system (Minucells and Minutissue, Germany). Medium was const...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Masungi C,Borremans C,Willems B,Mensch J,Van Dijck A,Augustijns P,Brewster ME,Noppe M

    更新日期:2004-10-01 00:00:00

  • Using Milling to Explore Physical States: The Amorphous and Polymorphic Forms of Sulindac.

    abstract::This article shows how milling can be used to explore the phase diagram of pharmaceuticals. This process has been applied to sulindac. A short milling has been found to trigger a polymorphic transformation between form II and form I upon heating which is not seen in the nonmilled material. This possibility was clearly...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Latreche M,Willart JF,Guerain M,Hédoux A,Danède F

    更新日期:2019-08-01 00:00:00

  • Interactions of cephalosporins and penicillins with nonpolar octadecylsilyl stationary phase.

    abstract::The capacity factors of several penicillins and cephalosporins, as well as those of 7-aminocephalosporanic acid, 6-aminopenicillanic acid, and 7-aminodeacetoxycephalosporanic acid, were determined at pH 2.5-7.5 with different methanol concentrations in the mobile phase. The influence of ionic strength on activity fact...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Salto F,Prieto JG,Alemany MT

    更新日期:1980-05-01 00:00:00

  • Antimicrobial properties of alkaloids from Xanthorhiza simplicissima.

    abstract::The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid be...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Okunade AL,Hufford CD,Richardson MD,Peterson JR,Clark AM

    更新日期:1994-03-01 00:00:00

  • Surface Tracking of Curcumin Amorphous Solid Dispersions Formulated by Binary Polymers.

    abstract::Herein, curcumin amorphous solid dispersions (Cur ASDs) were prepared using binary polymers (Eudragit EPO with polyvinylpyrrolidone K30 [EuD-PVP], Eudragit EPO with hydroxypropyl methylcellulose E50 [EuD-HPMC]) as excipient, and surface tracking of Cur ASDs was mainly addressed. Infrared spectroscopy, in situ Raman im...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Fan N,Lu T,Li J

    更新日期:2020-02-01 00:00:00

  • Video characterization of flume patterns of inhalation aerosols.

    abstract::An in vitro technique was developed to characterize the intermittent flume patterns associated with the short bursts of metered-dose aerosols. Two orthogonal video images are utilized to describe the complex shape and direction of the flume pattern. This technique facilitates the evaluation of components manufactured ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Miszuk S,Gupta BM,Chen FC,Clawans C,Knapp JZ

    更新日期:1980-06-01 00:00:00

  • Three-Dimensional Printing of Carbamazepine Sustained-Release Scaffold.

    abstract::Carbamazepine is the first-line anti-epileptic drug for focal seizures and generalized tonic-clonic seizures. Although sustained-release formulations exist, an initial burst of drug release is still present and this results in side effects. Zero-order release formulations reduce fluctuations in serum drug concentratio...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lim SH,Chia SM,Kang L,Yap KY

    更新日期:2016-07-01 00:00:00

  • Delivery of MUC1 mucin peptide by Poly(d,l-lactic-co-glycolic acid) microspheres induces type 1 T helper immune responses.

    abstract::Synthetic peptides corresponding to the variable tandem repeat domain of the cancer-associated antigen MUC1 mucin are candidates for cancer vaccines. In our investigation mice were immunized via subcutaneous injection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres containing a MUC1 mucin peptide. It was hy...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Newman KD,Sosnowski DL,Kwon GS,Samuel J

    更新日期:1998-11-01 00:00:00

  • Development of a nanofiltration process to improve the stability of a novel anti-MRSA carbapenem drug candidate.

    abstract::The benzenesulfonate salt of an anti-methicillin-resistant Staphylococcus aureus carbapenem antibiotic studied is a crystalline, nonhygroscopic powder which is stable at room temperature, making it an ideal compound for long-term storage. However, the limited aqueous solubility of this salt prohibits parenteral admini...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Antonucci V,Yen D,Kelly J,Crocker L,Dienemann E,Miller R,Almarrsson O

    更新日期:2002-04-01 00:00:00

  • Optimal PEGylation can improve the exposure of interferon in the lungs following pulmonary administration.

    abstract::The utility of inhaled protein therapeutics to treat lung-resident diseases is limited by protein degradation in the lungs and rapid clearance. This study therefore aimed to evaluate the impact of PEGylation on the lung and systemic exposure of interferon (IFN) α2 after intratracheal administration to rats. An inverse...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Mcleod VM,Chan LJ,Ryan GM,Porter CJ,Kaminskas LM

    更新日期:2015-04-01 00:00:00

  • Irreversible aggregation of recombinant bovine granulocyte-colony stimulating factor (bG-CSF) and implications for predicting protein shelf life.

    abstract::The kinetics of irreversible aggregation of bovine Granulocyte-Colony Stimulating Factor (bG-CSF) in solution were investigated as a function of temperature (T), concentration, and pH, and analyzed in terms of an Extended Lumry-Eyring model of protein aggregation proceeding via a non-native conformational state. In th...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Roberts CJ,Darrington RT,Whitley MB

    更新日期:2003-05-01 00:00:00

  • Effect of inorganic additives on solutions of nonionic surfactants III: CMC's and surface properties.

    abstract::Continuing work on the interaction of inorganic additives with nonionic surfactants in aqueous solution dealt with their effect on the CMC and surface tension. The surfactants were octoxynol and polyoxyethylated oleyl alcohol, containing an average of 9.5 and 10 ethylene oxide units, respectively. Their CMC values wer...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Schott H,Han SK

    更新日期:1976-07-01 00:00:00

  • Mechanisms of solvent evaporation encapsulation processes: prediction of solvent evaporation rate.

    abstract::The mechanism of organic solvent evaporation during microencapsulation and its role during microsphere hardening has been investigated. Evaporation and encapsulation studies were carried out in a jacketed beaker, filled with aqueous hardening solution, which was maintained at constant temperature and constant stirring...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wang J,Schwendeman SP

    更新日期:1999-10-01 00:00:00

  • Container Surfaces Control Initiation of Cavitation and Resulting Particle Formation in Protein Formulations After Application of Mechanical Shock.

    abstract::Mechanical shock may cause cavitation in vials containing liquid formulations of therapeutic proteins and generate protein aggregates and other particulates. To test whether common formulation components such as protein molecules, air bubbles, or polysorbate 20 (PS20) micelles might nucleate cavitation, a high-speed v...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wu H,Chisholm CF,Puryear M,Movafaghi S,Smith SD,Pokhilchuk Y,Lengsfeld CS,Randolph TW

    更新日期:2020-03-01 00:00:00

  • Direct nose-brain transport of benzoylecgonine following intranasal administration in rats.

    abstract::In our previous research, cocaine applied intranasally in rats diffused or was transported directly from the nasal cavity to the brain. However, the direct nose-brain cocaine transport only contributes to an initial increase in the relative cocaine brain exposure. In this study, we have determined the nose-brain trans...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chow HH,Anavy N,Villalobos A

    更新日期:2001-11-01 00:00:00

  • Plasma binding of benzodiazepines in humans.

    abstract::Plasma binding of chlordiazepoxide, diazepam, loraxepam, and oxazepam was determined by equilibrium dialysis in 20 male, healthy volunteers, 25-86 years old. A wide range of binding was observed, with the free fraction varying twofold for lorazepam, fourfold for chlordiazepoxide and diazepam, and over 20-fold for oxa...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Johnson RF,Schenker S,Roberts RK,Desmond PV,Wilkinson GR

    更新日期:1979-10-01 00:00:00

  • Pharmaceutical impurity identification: a case study using a multidisciplinary approach.

    abstract::A multidisciplinary team approach to identify pharmaceutical impurities is presented in this article. It includes a representative example of the methodology. The first step is to analyze the sample by LC-MS. If the structure of the unknown impurity cannot be conclusively determined by LC-MS, LC-NMR is employed. If th...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Alsante KM,Boutros P,Couturier MA,Friedmann RC,Harwood JW,Horan GJ,Jensen AJ,Liu Q,Lohr LL,Morris R,Raggon JW,Reid GL,Santafianos DP,Sharp TR,Tucker JL,Wilcox GE

    更新日期:2004-09-01 00:00:00

  • Design of folic acid-conjugated nanoparticles for drug targeting.

    abstract::The new concept developed in this study is the design of poly(ethylene glycol) (PEG)-coated biodegradable nanoparticles coupled to folic acid to target the folate-binding protein; this molecule is the soluble form of the folate receptor that is overexpressed on the surface of many tumoral cells. For this purpose, a no...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Stella B,Arpicco S,Peracchia MT,Desmaële D,Hoebeke J,Renoir M,D'Angelo J,Cattel L,Couvreur P

    更新日期:2000-11-01 00:00:00

  • Determination of the permeability characteristics of two sulfenamide prodrugs of linezolid across Caco-2 cells.

    abstract::The purpose of this work was to study the permeability of two relatively lipophilic sulfenamide prodrugs of linezolid (clogP 0.85), N-(phenylthio)linezolid (1, clogP 2.77) and N-[(2-ethoxycarbonyl)ethylthio]linezolid (2, clogP 1.43), across Caco-2 cell monolayers. Both prodrugs were found to convert to linezolid in th...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Nti-Addae KW,Guarino VR,Dalwadi G,Stella VJ

    更新日期:2012-09-01 00:00:00

  • Effect of benzalkonium chloride/EDTA on the ocular bioavailability of ketorolac tromethamine following ocular instillation to normal and de-epithelialized corneas of rabbits.

    abstract::This study was designed to examine the effect of benzalkonium chloride/ethylenediaminetetraacetic acid (BAK/EDTA) on the ocular bioavailability (Focular) of ketorolac tromethamine after ocular instillation to normal and de-epithelialized corneas of rabbits both in vitro and in vivo. The in vitro Focular of the formula...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Madhu C,Rix PJ,Shackleton MJ,Nguyen TG,Tang-Liu DD

    更新日期:1996-04-01 00:00:00

  • Synthesis and biological evaluation of gem-dichlorocyclopropyl and cyclopropyl analogs of stilbene congeners as potential antiestrogens.

    abstract::A series of gem-cichlorocyclopropyl and cyclopropyl analogs of stilbene congeners was synthesized and examined for estrogenic and antiestrogenic activity using the uterotropic assay in the immature mouse. The relative receptor affinity in vitro was determined by measuring [3H]estradiol displacement from the rat uterin...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Stobaugh JF,Magarian RA,Pento JT

    更新日期:1982-10-01 00:00:00

  • Drug delivery trends in clinical trials and translational medicine: evaluation of pharmacokinetic properties in special populations.

    abstract::In spite of the recent advances in technology to optimize the absorption, distribution, metabolism and elimination (ADME) properties of new and promising medicinal products to reduce clinical failures, the investigation of drug disposition in the pediatric and elderly populations continues to be under evaluated. With ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章,评审


    authors: Chien JY,Ho RJ

    更新日期:2011-01-01 00:00:00

  • A Measurement and Modeling Study of Hair Partition of Neutral, Cationic, and Anionic Chemicals.

    abstract::Various neutral, cationic, and anionic chemicals contained in hair care products can be absorbed into hair fiber to modulate physicochemical properties such as color, strength, style, and volume. For environmental safety, there is also an interest in understanding hair absorption to wide chemical pollutants. There hav...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Li L,Yang S,Chen T,Han L,Lian G

    更新日期:2018-04-01 00:00:00

  • Preclinical pharmacokinetic evaluation of resveratrol trimethyl ether in sprague-dawley rats: the impacts of aqueous solubility, dose escalation, food and repeated dosing on oral bioavailability.

    abstract::Resveratrol trimethyl ether (trans-3,5,4'-trimethoxystilbene, RTE) is a naturally occurring and pharmacologically active resveratrol derivative. To evaluate its suitability as a drug candidate, a pharmacokinetic study was carried out in Sprague-Dawley rats with the emphasis to identify the impact of aqueous solubility...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lin HS,Ho PC

    更新日期:2011-10-01 00:00:00

  • Antitumor agents: structure--activity relationships in tenulin series.

    abstract::Systematic structural modifications were performed on the natural sesquiterpene lactone tenulin to define those groupings essential to, or significant in, its in vivo antitumor activity. Accordingly, the following tenulin analogs were prepared: dihydrotenulin, 2,3-epoxytenulin, isotenulin, dihydroisotenulin, 2,3-epoxy...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Waddell TG,Austin AM,Cochran JW,Gerhart KG,Hall IH,Lee KH

    更新日期:1979-06-01 00:00:00

  • Preparation and characterization of Apo2L/TNF-related apoptosis-inducing ligand-loaded human serum albumin nanoparticles with improved stability and tumor distribution.

    abstract::Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received considerable attention as a potential anticancer agent. However, recombinant Apo2L/TRAIL has several limitations, which include a weak pharmacokinetic profile, namely, a short biological half-life and rapid renal clearance, and an inability t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kim TH,Jiang HH,Youn YS,Park CW,Lim SM,Jin CH,Tak KK,Lee HS,Lee KC

    更新日期:2011-02-01 00:00:00

  • Physical stability comparisons of IgG1-Fc variants: effects of N-glycosylation site occupancy and Asp/Gln residues at site Asn 297.

    abstract::The structural integrity and conformational stability of various IgG1-Fc proteins produced from the yeast Pichia pastoris with different glycosylation site occupancy (di-, mono-, and nonglycosylated) were determined. In addition, the physical stability profiles of three different forms of nonglycosylated Fc molecules ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Alsenaidy MA,Okbazghi SZ,Kim JH,Joshi SB,Middaugh CR,Tolbert TJ,Volkin DB

    更新日期:2014-06-01 00:00:00

  • Fcγ Receptor Activation by Human Monoclonal Antibody Aggregates.

    abstract::Protein aggregates are a potential risk factor for immunogenicity. The measurement, characterization, and control of protein aggregates in drug products are indispensable for the development of biopharmaceuticals, including therapeutic mAbs. In this study, Fcγ receptor (FcγR)-expressing reporter cell lines were used t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Tada M,Aoyama M,Ishii-Watabe A

    更新日期:2020-01-01 00:00:00

  • Structural functions of the sweet pharmacophore.

    abstract::The relative sweetness, onset times, and durations of response of D-glucose, D-xylose, D-quinovose, D-galactose, L-arabinose, and D-fucose were determined at four temperatures. The results can be interpreted by simple concepts of intramolecular hydrogen bonding which indicate that the so-called gamma-function of the t...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Birch GG,Dziedzic SZ,Shallenberger RS,Lindley MG

    更新日期:1981-03-01 00:00:00

  • Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    abstract::Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chen L,Sloey C,Zhang Z,Bondarenko PV,Kim H,Ren D,Kanapuram S

    更新日期:2015-02-01 00:00:00