Development of a sensitive activity assay for high-volume evaluation of human renin inhibitory peptides in rat serum: results with U-71,038.

Abstract:

:A sensitive activity assay for high volume evaluation of human renin inhibitory peptides (RIPs) in rat sera (range 2-80 ng/ml) was developed based on the low affinity of RIPs to rat renin and their high affinity to human renin. The utility of this activity assay was tested by measuring concentrations of a human RIP, U-71,038 (BOC-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]Val-Ile-Amp), in rat sera, determined by the activity assay, by a sensitive radioimmunoassay (RIA), and by tracking tritiated drug. Rats were given radiolabeled drug as an intravenous bolus, and blood samples were collected at various times after dosing. The serum level of U-71,038 equivalents was determined by the three techniques. Whole blood was also counted for total radioactivity to evaluate the potential for U-71,038 incorporation into red blood cells. Results from the three serum assays indicate good agreement between the calculated U-71,038 equivalents for the 30 min and 1 hr collection times. The 2 and 4 hr collection times show excellent agreement for the activity assay and RIA; [3H]-U-71,038 determinations gave substantially higher values. Serum levels for U-71,038 determined 30 min after dosing averaged less than 300 ng equivalents/ml suggesting that less than 1% of the administered dose was in the systemic circulation at that time. Thus, U-71,038 was rapidly cleared. At the 4 hr collection time, the level of U-71,038 equivalents, as determined by activity assay and RIA, was ten times the in vitro IC50 for the renin inhibitory activity of U-71,038.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Ruwart MJ,Sharma SK,Harris DW,Lakings DB,Rush BD,Wilkinson KF,Cornette JC,Evans DB,Friis JM,Cook KJ

doi

10.1023/a:1015883709275

subject

Has Abstract,Author List Incomplete

pub_date

1990-04-01 00:00:00

pages

407-10

issue

4

eissn

0724-8741

issn

1573-904X

journal_volume

7

pub_type

杂志文章
  • A study on structural and diffusion properties of porcine stratum corneum based on very small angle neutron scattering data.

    abstract:PURPOSE:Generation of valuable information about the biphasic geometrical configuration of porcine stratum corneum from Very Small Angle Neutron Scattering (VSANS) data and investigation of its effect on the corresponding effective diffusivity. METHODS:Spectra of porcine stratum corneum are mathematically transformed ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1026453628800

    authors: Charalambopoulou GC,Karamertzanis P,Kikkinides ES,Stubos AK,Kanellopoulos NK,Papaioannou AT

    更新日期:2000-09-01 00:00:00

  • Saquinavir Loaded Acetalated Dextran Microconfetti - a Long Acting Protease Inhibitor Injectable.

    abstract:PURPOSE:Since the adoption of highly active antiretroviral therapy, HIV disease progression has slowed across the world; however, patients are often required to take multiple medications daily of poorly bioavailable drugs via the oral route, leading to gastrointestinal irritation. Recently, long acting antiretroviral i...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-016-1936-y

    authors: Collier MA,Gallovic MD,Bachelder EM,Sykes CD,Kashuba A,Ainslie KM

    更新日期:2016-08-01 00:00:00

  • The relationship between the glass transition temperature and the water content of amorphous pharmaceutical solids.

    abstract::The glass transition temperature of an amorphous pharmaceutical solid is a critical physical property which can dramatically influence its chemical stability, physical stability, and viscoelastic properties. Water frequently acts as a potent plasticizer for such materials, and since many amorphous solids spontaneously...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018941810744

    authors: Hancock BC,Zografi G

    更新日期:1994-04-01 00:00:00

  • Solid-state emulsions: the effects of process and storage conditions.

    abstract::The effects of process and storage conditions of solid-state emulsions were studied. Oil-in-water emulsions may be prepared from solid state emulsions by adding an aqueous phase to the solid. Solid-state emulsions are prepared by processing an oil phase and an aqueous solution of matrix material via a solvent removal ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018983227234

    authors: Shively ML,Myers S

    更新日期:1993-07-01 00:00:00

  • Delivery of HSP90 Inhibitor Using Water Soluble Polymeric Conjugates with High Drug Payload.

    abstract:PURPOSE:HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-017-2249-5

    authors: Suárez Del Pino JA,Kolhatkar R

    更新日期:2017-12-01 00:00:00

  • Assessment of the lateral diffusion and penetration of topically applied drugs in humans using a novel concentric tape stripping design.

    abstract:PURPOSE:To determine the extent of lateral spread and stratum corneum (SC) penetration of caffeine (CAF), hydrocortisone (HC) and ibuprofen (IBU) using a novel concentric tape stripping technique. METHOD:Ethanolic solutions of CAF, HC or IBU were applied to the forearm of 8 volunteers. At various time points, 10 succe...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-012-0731-7

    authors: Gee CM,Nicolazzo JA,Watkinson AC,Finnin BC

    更新日期:2012-08-01 00:00:00

  • Investigation of the gastrointestinal transit and in vivo drug release of isosorbide-5-nitrate pellets.

    abstract::An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016423404636

    authors: Fischer W,Boertz A,Davis SS,Khosla R,Cawello W,Sandrock K,Cordes G

    更新日期:1987-12-01 00:00:00

  • Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs.

    abstract:PURPOSE:The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs. METHODS:Preparation of the bicarbonate-containing dissolution medium was monitored by use...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1026147620304

    authors: McNamara DP,Whitney KM,Goss SL

    更新日期:2003-10-01 00:00:00

  • Nasal Administration of Cationic Nanoemulsions as Nucleic Acids Delivery Systems Aiming at Mucopolysaccharidosis Type I Gene Therapy.

    abstract:PURPOSE:This study demonstrates the nasal administration (NA) of nanoemulsions complexed with the plasmid encoding for IDUA protein (pIDUA) as an attempt to reach the brain aiming at MPS I gene therapy. METHODS:Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE-PEG (NE-PEG) were prepared by high-pressure homogen...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-018-2503-5

    authors: Schuh RS,Bidone J,Poletto E,Pinheiro CV,Pasqualim G,de Carvalho TG,Farinon M,da Silva Diel D,Xavier RM,Baldo G,Matte U,Teixeira HF

    更新日期:2018-09-26 00:00:00

  • Quantitative assessment of intestinal first-pass metabolism of oral drugs using portal-vein cannulated rats.

    abstract:PURPOSE:To evaluate the impact of intestinal first-pass metabolism (Fg) by cytochrome P4503A (CYP3A) and uridine 5'-diphosphate-glucuronosyltransferases (UGT) on in vivo oral absorption of their substrate drugs. METHODS:CYP3A and UGT substrates were orally administered to portal-vein cannulated (PV) rats to evaluate t...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-014-1489-x

    authors: Matsuda Y,Konno Y,Hashimoto T,Nagai M,Taguchi T,Satsukawa M,Yamashita S

    更新日期:2015-02-01 00:00:00

  • Freeze-concentration separates proteins and polymer excipients into different amorphous phases.

    abstract:PURPOSE:To study the miscibility of proteins and polymer excipients in frozen solutions and freeze-dried solids as protein formulation models. METHODS:Thermal profiles of frozen solutions and freeze-dried solids containing various proteins (lysozyme, ovalbumin, BSA), nonionic polymers (Ficoll, polyvinylpyrrolidone [PV...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1026412107574

    authors: Izutsu K,Kojima S

    更新日期:2000-10-01 00:00:00

  • A novel evaluation method of gastric mucoadhesive property in vitro and the mucoadhesive mechanism of tetracycline-sucralfate acidic complex for eradication of Helicobacter pylori.

    abstract:PURPOSE:The gastric mucoadhesive property of tetracycline-sucralfate acidic complex (CO) was evaluated by using a novel method in vitro to compare with the in vivo test. The mucoadhesive mechanism of the acidic complex was also studied. METHODS:The gastric mucosa removed from a rat was placed covering the end of a plu...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/B:PHAM.0000019293.57927.7f

    authors: Higo S,Ori K,Takeuchi H,Yamamoto H,Hino T,Kawashima Y

    更新日期:2004-03-01 00:00:00

  • Influence of the Size of Cohorts in Adaptive Design for Nonlinear Mixed Effects Models: An Evaluation by Simulation for a Pharmacokinetic and Pharmacodynamic Model for a Biomarker in Oncology.

    abstract:PURPOSE:In this study we aimed to evaluate adaptive designs (ADs) by clinical trial simulation for a pharmacokinetic-pharmacodynamic model in oncology and to compare them with one-stage designs, i.e., when no adaptation is performed, using wrong prior parameters. METHODS:We evaluated two one-stage designs, ξ0 and ξ*, ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-015-1693-3

    authors: Lestini G,Dumont C,Mentré F

    更新日期:2015-10-01 00:00:00

  • Measuring The Bipolar Charge Distributions of Fine Particle Aerosol Clouds of Commercial PMDI Suspensions Using a Bipolar Next Generation Impactor (bp-NGI).

    abstract:PURPOSE:To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). M...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-018-2544-9

    authors: Rowland M,Cavecchi A,Thielmann F,Kulon J,Shur J,Price R

    更新日期:2018-11-26 00:00:00

  • Enhancement of nasal salmon calcitonin absorption by lauroylcarnitine chloride in rats.

    abstract:PURPOSE:We investigated optimum formulation characteristics in the nasal absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines. METHODS:Nasal sCT formulations were administered to anesthetized rats. Plasma calcium level was measured and pharmacological bioavailability (P.bioav) was calculated. RESU...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016051600828

    authors: Kagatani S,Shinoda T,Fukui M,Ohmura T,Hasumi S,Sonobe T

    更新日期:1996-05-01 00:00:00

  • Receptor-mediated magnetic carriers: basis for targeting.

    abstract::A new magnetic microsphere carrier has been formulated that may localize drugs by both biochemical and physical means. The microspheres, prepared from the polysaccharide chitosan, are designed to bind to anionic glycosaminoglycan receptors on the surface of capillary endothelial cells. The microspheres were formulated...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015978704810

    authors: Gallo JM,Hassan EE

    更新日期:1988-05-01 00:00:00

  • Efficacy of Optimized Treatment Protocol Using LAU-7b Formulation against Ovalbumin (OVA) and House Dust Mite (HDM) -Induced Allergic Asthma in Atopic Hyperresponsive A/J Mice.

    abstract:PURPOSE:To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS:We used two allergens (OVA and HDM) to induce asthma in mou...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-019-2743-z

    authors: Youssef M,De Sanctis JB,Kanagaratham C,Tao S,Ahmed E,Radzioch D

    更新日期:2020-01-08 00:00:00

  • Evaluation of temperature-sensitive, indocyanine green-encapsulating micelles for noninvasive near-infrared tumor imaging.

    abstract:PURPOSE:Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To addre...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-010-0190-y

    authors: Kim TH,Chen Y,Mount CW,Gombotz WR,Li X,Pun SH

    更新日期:2010-09-01 00:00:00

  • Study on pulmonary delivery of salmon calcitonin in rats: effects of protease inhibitors and absorption enhancers.

    abstract::Effects of protease inhibitors and absorption enhancers on the absorption of salmon calcitonin (sCT) were evaluated after intratracheal coadministration to rats using the plasma Ca level as an index. Remarkable absorption enhancement could be attained with unsaturated fatty acids such as oleic acid and polyoxyethylene...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018926007902

    authors: Kobayashi S,Kondo S,Juni K

    更新日期:1994-09-01 00:00:00

  • Correlation of partitioning of nitroimidazoles in the n-octanol/saline and liposome systems with pharmacokinetic parameters and quantitative structure-activity relationships (QSAR).

    abstract::The partitioning of a series of nine nitroimidazole drugs in liposomes (log Km) of various compositions has been determined and compared to their partitioning in the n-octanol/saline system (log K) at 30 degrees C. The log Km ranged from 1.5 to 0.5 and was three- to fourfold greater than the log K; further, the linear...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015931431817

    authors: Betageri GV,Rogers JA

    更新日期:1989-05-01 00:00:00

  • New respirable and fast dissolving itraconazole dry powder composition for the treatment of invasive pulmonary aspergillosis.

    abstract:PURPOSE:Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were optimized for aerodynamic and dissolution properties and contained excipients that are acceptable for inhalation. METHODS:The DPI were produced by spray drying solutions. The drug content, crystallinity state, and morphological evaluation of ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-012-0779-4

    authors: Duret C,Wauthoz N,Sebti T,Vanderbist F,Amighi K

    更新日期:2012-10-01 00:00:00

  • Psychometric evaluation of measures of organizational commitment and intention to quit among pharmaceutical scientists.

    abstract::This study utilized different statistical techniques to evaluate the reliability (internal consistency) and the discriminant validity of the most widely used measures of organizational commitment and intention to quit (the employing organization). Data were obtained from a national mail survey of members of the Americ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018930718979

    authors: Kong SX,Wertheimer AI,Serradell J,McGhan WF

    更新日期:1994-01-01 00:00:00

  • Rapid-Acting and Human Insulins: Hexamer Dissociation Kinetics upon Dilution of the Pharmaceutical Formulation.

    abstract:PURPOSE:Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions. METHODS:Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering....

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-017-2233-0

    authors: Gast K,Schüler A,Wolff M,Thalhammer A,Berchtold H,Nagel N,Lenherr G,Hauck G,Seckler R

    更新日期:2017-11-01 00:00:00

  • Antiangiogenic effect of docetaxel and everolimus as individual and dual-drug-loaded micellar nanocarriers.

    abstract:PURPOSE:The in vitro inhibitory effect of Docetaxel (DTX) and Everolimus (EVR) alone and together in poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) nanocarriers on angiogenic processes and acute toxicity in mice was evaluated. METHODS:PEG-b-PLA DTX and/or EVR nanocarriers were characterized for size, dr...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-013-1188-z

    authors: Mishra GP,Doddapaneni BS,Nguyen D,Alani AW

    更新日期:2014-03-01 00:00:00

  • In vivo fluorescence imaging of IgG1 aggregates after subcutaneous and intravenous injection in mice.

    abstract:PURPOSE:To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC) and intravenous (IV) administration in mice and measure their propensity to stimulate an early immune response. METHODS:A human mAb (IgG1) was fluorescently labeled, aggregated by agitation stress and injected in SKH1 mice through SC and ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-013-1154-9

    authors: Filipe V,Que I,Carpenter JF,Löwik C,Jiskoot W

    更新日期:2014-01-01 00:00:00

  • Poly-L-arginine enhances paracellular permeability via serine/threonine phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit nasal epithelium.

    abstract:PURPOSE:The purpose of the present study is to explore whether a poly-L-arginine (poly-L-Arg)-induced increase in tight junctions (TJ) permeability of fluorescein isothiocyanate-labeled dextran (MW 4.4 kDa, FD-4) is associated with the Ca2+-dependent signaling and occurs following the phosphorylation/dephosphorylation ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/b:pham.0000003383.86238.d1

    authors: Ohtake K,Maeno T,Ueda H,Ogihara M,Natsume H,Morimoto Y

    更新日期:2003-11-01 00:00:00

  • Utility of hydroxypropylmethylcellulose acetate succinate (HPMCAS) for initiation and maintenance of drug supersaturation in the GI milieu.

    abstract:PURPOSE:To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability. METHODS:A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-009-9852-z

    authors: Curatolo W,Nightingale JA,Herbig SM

    更新日期:2009-06-01 00:00:00

  • Morphine blood-brain barrier transport is influenced by probenecid co-administration.

    abstract:PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1023250900462

    authors: Tunblad K,Jonsson EN,Hammarlund-Udenaes M

    更新日期:2003-04-01 00:00:00

  • Intranasal delivery--modification of drug metabolism and brain disposition.

    abstract::Intranasal route continues to be one of the main focuses of drug delivery research. Although it is generally perceived that the nasal route could avoid the first-pass metabolism in liver and gastrointestinal tract, the role of metabolic conversions in systemic and brain-targeted deliveries of the parent compounds and ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-010-0127-5

    authors: Wong YC,Zuo Z

    更新日期:2010-07-01 00:00:00

  • Bioavailability and pharmacokinetics of a new sustained-release potassium chloride tablet.

    abstract::The bioavailability of a new sustained-release potassium chloride (KCl) tablet, designed for once-a-day dosing, was compared to a KCl elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016438413297

    authors: Betlach CJ,Arnold JD,Frost RW,Leese PT,Gonzalez MA

    更新日期:1987-10-01 00:00:00