A pharmacokinetic model of intravenously administered hyaluronan in sheep.


:Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA concentration by injection of a 3H-labeled tracer and at a very high concentration by an i.v. infusion of unlabeled HA and simultaneous injection of a tracer dose of 3H-labeled HA. At a normal plasma HA concentration (0.12 +/- 0.05 microgram/ml; range, 0.072-0.228 microgram/ml), the apparent T 1/2 of 3H-HA was 5.3 +/- 1.1 min (range, 3.3-6.5 min). At higher plasma concentrations (range, 1.83-3.35 micrograms/ml), the apparent T 1/2 was considerably prolonged (range, 18.2-43.5 min). A one-compartment, nonlinear model was fitted to data obtained from the bolus-infusion study of unlabeled HA. The Michaelis-Menten constant, Km, was 0.12 +/- 0.04 microgram/ml, indicating that a deviation from linear kinetics will occur when the normal plasma concentration is exceeded. The Vmax was 0.062 +/- 0.009 microgram/ml/min. Three-dimensional surface plots showed that the plasma HA concentration and the total hepatic plasma flow influence the apparent metabolic clearance, extraction ratio, turnover, and T 1/2 of intravenously injected hyaluronan. There was a high correlation between T 1/2 as measured by the injected 3H-HA and T 1/2 calculated from the model (r = 0.96).


Pharm Res


Pharmaceutical research


Lebel L,Fraser JR,Kimpton WS,Gabrielsson J,Gerdin B,Laurent TC




Has Abstract


1989-08-01 00:00:00












  • Selective contrast enhancement of individual Alzheimer's disease amyloid plaques using a polyamine and Gd-DOTA conjugated antibody fragment against fibrillar Abeta42 for magnetic resonance molecular imaging.

    abstract:PURPOSE:The lack of an in vivo diagnostic test for AD has prompted the targeting of amyloid plaques with diagnostic imaging probes. We describe the development of a contrast agent (CA) for magnetic resonance microimaging that utilizes the F(ab')2 fragment of a monoclonal antibody raised against fibrillar human Abeta42 ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ramakrishnan M,Wengenack TM,Kandimalla KK,Curran GL,Gilles EJ,Ramirez-Alvarado M,Lin J,Garwood M,Jack CR Jr,Poduslo JF

    更新日期:2008-08-01 00:00:00

  • Molecular structure and dynamics of cis(Z)-and trans(E)-flupenthixol and clopenthixol.

    abstract::The three-dimensional structures and molecular electrostatic potentials of the cis(Z) and trans(E)-isomers of flupenthixol and clopenthixol were examined by computer graphics and molecular mechanical and quantum mechanical calculations, and their internal molecular motions were studied by molecular dynamics simulation...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sylte I,Dahl SG

    更新日期:1991-04-01 00:00:00

  • Immune modulation by adjuvants combined with diphtheria toxoid administered topically in BALB/c mice after microneedle array pretreatment.

    abstract:PURPOSE:In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. METHODS:TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ding Z,Van Riet E,Romeijn S,Kersten GF,Jiskoot W,Bouwstra JA

    更新日期:2009-07-01 00:00:00

  • Characterization of the mechanism of zidovudine uptake by rat conditionally immortalized syncytiotrophoblast cell line TR-TBT.

    abstract:PURPOSE:To characterize the uptake mechanism of zidovudine (AZT), a nucleoside reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT 18d-1 cell line previously established by our group. MATERIALS AND METHODS:The effects of several transporter inhibitors on the initial and steady-state apical u...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sai Y,Nishimura T,Shimpo S,Chishu T,Sato K,Kose N,Terasaki T,Mukai C,Kitagaki S,Miyakoshi N,Kang YS,Nakashima E

    更新日期:2008-07-01 00:00:00

  • Access to the CNS: Biomarker Strategies for Dopaminergic Treatments.

    abstract::Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multipl...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审


    authors: van den Brink WJ,Palic S,Köhler I,de Lange ECM

    更新日期:2018-02-15 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


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

    更新日期:2014-03-01 00:00:00

  • Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives.

    abstract::Pharmacokinetic/pharmacodynamic (PK/PD)-modeling links dose-concentration relationships (PK) and concentration-effect relationships (PD), thereby facilitating the description and prediction of the time course of drug effects resulting from a certain dosing regimen. PK/PD-modeling approaches can basically be distinguis...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Derendorf H,Meibohm B

    更新日期:1999-02-01 00:00:00

  • Sialic Acid-Engineered IL4-10 Fusion Protein is Bioactive and Rapidly Cleared from the Circulation.

    abstract:PURPOSE:Modulating sialylation of therapeutic glycoproteins may be used to influence their clearance and systemic exposure. We studied the effect of low and high sialylated IL4-10 fusion protein (IL4-10 FP) on in vitro and in vivo bioactivity and evaluated the effect of differential sialylation on pharmacokinetic param...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Steen-Louws C,Boross P,Prado J,Meeldijk J,Langenhorst JB,Huitema ADR,den Hartog MT,Boon L,Lafeber FPJG,Hack CE,Eijkelkamp N,Popov-Celeketic J

    更新日期:2019-12-26 00:00:00

  • Role of viscosity in influencing the glass-forming ability of organic molecules from the undercooled melt state.

    abstract:PURPOSE:Understanding the critical factors governing the crystallization tendency of organic compounds is vital when assessing the feasibility of an amorphous formulation to improve oral bioavailability. The objective of this study was to investigate potential links between viscosity and crystallization tendency for or...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Baird JA,Santiago-Quinonez D,Rinaldi C,Taylor LS

    更新日期:2012-01-01 00:00:00

  • Column-switching high-performance liquid chromatography for on-line simultaneous determination and resolution of enantiomers of verapamil and its metabolites.

    abstract::An on-line simultaneous assay for the enantiomers of verapamil (VA) and its three metabolites in plasma was developed with column-switching HPLC. This system consists of an ovomucoid protein chiral stationary phase coupled to an achiral reversed-phase column via a dilution tube and a trapping column. The reversed-phas...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Oda Y,Asakawa N,Kajima T,Yoshida Y,Sato T

    更新日期:1991-08-01 00:00:00

  • Bioactive-Chylomicrons for Oral Lymphatic Targeting of Berberine Chloride: Novel Flow-Blockage Assay in Tissue-Based and Caco-2 Cell Line Models.

    abstract:PURPOSE:To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS:Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model an...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Elsheikh MA,Elnaggar YSR,Otify DY,Abdallah OY

    更新日期:2018-01-05 00:00:00

  • Relationship between drug percolation threshold and particle size in matrix tablets.

    abstract:PURPOSE:Since a previous qualitative study carried out by us showed the existence of an important influence of the particle size on the percolation thresholds and taking into account that the existing theoretical models can only provide qualitative explanation to this influence, the purpose of this work is to carry out...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Caraballo I,Millan M,Rabasco AM

    更新日期:1996-03-01 00:00:00

  • A novel topoisomerase II poison GL331 preferentially induces DNA cleavage at (C/G)T sites and can cause telomere DNA damage.

    abstract:PURPOSE:Topoisomerase II (Topo II) preferentially cuts DNA at alternating purine-pyrimidine repeats. Different Topo II poisons may affect Topo II to produce distinct drug-specific DNA cleavage patterns. GL331 is a new podophyllotoxin derivative exhibiting potent Topo II-poisoning activity. Therefore, the sequence selec...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Lee CC,Huang TS

    更新日期:2001-06-01 00:00:00

  • Mishandling of the therapeutic peptide glucagon generates cytotoxic amyloidogenic fibrils.

    abstract:PURPOSE:Some therapeutic peptides exhibit amyloidogenic properties that cause insolubility and cytotoxicity against neuronal cells in vitro. Here, we characterize the conformational change in monomeric therapeutic peptide to its fibrillar aggregate in order to prevent amyloidogenic formation during clinical application...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Onoue S,Ohshima K,Debari K,Koh K,Shioda S,Iwasa S,Kashimoto K,Yajima T

    更新日期:2004-07-01 00:00:00

  • Exploring Variation in Known Pharmacogenetic Variants and its Association with Drug Response in Different Mexican Populations.

    abstract:PURPOSE:Information on genetic variants that affect the pharmacokinetics and pharmacodynamics (PK/PD) of drugs in different populations from Mexico is still an ongoing endeavor. Here, we investigate allele frequencies on pharmacogenetic targets in Mexican Mestizos and Natives from three different States and its associa...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Gonzalez-Covarrubias V,Martínez-Magaña JJ,Coronado-Sosa R,Villegas-Torres B,Genis-Mendoza AD,Canales-Herrerias P,Nicolini H,Soberón X

    更新日期:2016-11-01 00:00:00

  • Heparin-paclitaxel conjugates using mixed anhydride as intermediate: synthesis, influence of polymer structure on drug release, anticoagulant activity and in vitro efficiency.

    abstract:PURPOSE:The heparin-paclitaxel conjugates using amino acid as linker (HD2), with low anticoagulant activity, the similar anticancer activity as paclitaxel, offer great potential for further investigation. METHODS:Two types of heparin-paclitaxel conjugates (HD) have been developed, in which O-acetylated heparin as carr...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Wang Y,Xin D,Liu K,Xiang J

    更新日期:2009-04-01 00:00:00

  • Functional identification of a novel transport system for endogenous and synthetic opioid peptides in the rabbit conjunctival epithelial cell line CJVE.

    abstract:PURPOSE:To investigate whether conjunctival epithelial cells express transport processes for opioid peptides. METHODS:We monitored the uptake of [(3)H]deltorphin II and [(3)H]DADLE, two hydrolysis-resistant synthetic opioid peptides, in the rabbit conjunctival epithelial cell line CJVE and elucidated the characteristi...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ananth S,Karunakaran S,Martin PM,Nagineni CN,Hooks JJ,Smith SB,Prasad PD,Ganapathy V

    更新日期:2009-05-01 00:00:00

  • Transepithelial transport of insulin: I. Insulin degradation by insulin-degrading enzyme in small intestinal epithelium.

    abstract:PURPOSE:The purpose of this study was to determine the existence of insulin-degrading enzyme (EC (IDE) in rat intestinal enterocytes. METHODS:Subcellular fractionation, biochemical characterization, immunoprecipitation, and western blots were employed. RESULTS:Insulin-degrading activity was localized in th...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Bai JP,Chang LL

    更新日期:1995-08-01 00:00:00

  • Human jejunal permeability of cyclosporin A: influence of surfactants on P-glycoprotein efflux in Caco-2 cells.

    abstract:PURPOSE:The purpose of this work was to determine the jejunal permeability of cyclosporin A (CsA) in humans and whether formulation variables modulate the effects of P-glycoprotein (P-gp) on the permeability of CsA in Caco-2 cells. METHODS:A solution containing CsA, phenylalanine, propranolol, polyethyleneglycol (PEG)...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Chiu YY,Higaki K,Neudeck BL,Barnett JL,Welage LS,Amidon GL

    更新日期:2003-05-01 00:00:00

  • Change of phase-solubility behavior by gamma-cyclodextrin derivatization.

    abstract::The effect of γ-cyclodextrin and its four derivatives on the solubility of progesterone in phosphate buffer pH 7.4 was investigated. γ-Cyclodextrin forms a complex precipitating from solution at low cyclodextrin concentrations. No precipitation of complexes was observed with the γ-cyclodextrin derivatives. This change...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Müller BW,Brauns U

    更新日期:1985-11-01 00:00:00

  • p-Aminohippurate transport at the apical membrane in the OK kidney epithelial cell line.

    abstract:PURPOSE:We investigated the characteristics of transport of an organic anion, p-aminohippurate (PAH), at the apical membrane in a kidney epithelial cell line OK. METHODS:Efflux and uptake of [14C]PAH across the apical membrane were measured using OK cell monolayers grown on microporous membrane filters. RESULTS:PAH e...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Habu Y,Yano I,Hashimoto Y,Saito H,Inui K

    更新日期:2002-12-01 00:00:00

  • Nebulization of fluids of different physicochemical properties with air-jet and ultrasonic nebulizers.

    abstract:PURPOSE:Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective "filtering" effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and su...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: McCallion ON,Taylor KM,Thomas M,Taylor AJ

    更新日期:1995-11-01 00:00:00

  • D-glucose triggers multidrug resistance-associated protein (MRP)-mediated secretion of fluorescein across rat jejunum in vitro.

    abstract:PURPOSE:To examine the transport characteristics of the multidrug resistance-associated protein (MRP) substrate fluorescein across the isolated rat small intestinal segments. METHODS:The transport of fluorescein was studied in side-by-side diffusion chambers under short-circuited conditions at physiological pH. RESUL...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Legen I,Kristl A

    更新日期:2004-04-01 00:00:00

  • Route of administration and sex differences in the pharmacokinetics of aspirin, administered as its lysine salt.

    abstract::One thousand milligrams of aspirin, as its lysine salt was administered intravenously, orally, and intramuscularly to nine male and nine female young healthy adult volunteers. After intravenous injection mean (+/- SD) values of clearance, steady-state volume of distribution, and terminal half-life were 12.2 +/- 2.2 ml...

    journal_title:Pharmaceutical research

    pub_type: 临床试验,杂志文章


    authors: Aarons L,Hopkins K,Rowland M,Brossel S,Thiercelin JF

    更新日期:1989-08-01 00:00:00

  • Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor.

    abstract:PURPOSE:This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. METHODS:Plasma samples were collected at 1.5, 4, and 10 h after first oral ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sung JW,Yun HY,Park S,Kim YJ,Yee J,Lee KE,Song B,Chung JE,Gwak HS

    更新日期:2020-01-28 00:00:00

  • Synthesis and Characterization of Nanocomposite Microparticles (nCmP) for the Treatment of Cystic Fibrosis-Related Infections.

    abstract:PURPOSE:Pulmonary antibiotic delivery is recommended as maintenance therapy for cystic fibrosis (CF) patients who experience chronic infections. However, abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs mucus penetration and limits the efficacy of inhaled antibiotics. To overcom...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Wang Z,Meenach SA

    更新日期:2016-08-01 00:00:00

  • Characterizing the expression of CYP3A4 and efflux transporters (P-gp, MRP1, and MRP2) in CYP3A4-transfected Caco-2 cells after induction with sodium butyrate and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.

    abstract:PURPOSE:To examine the changes in expression levels of CYP3A4 and efflux transporters in CYP3A4-transfected Caco-2 (colon carcinoma) cells in the presence of the inducers sodium butyrate (NaB) and 12-O-tetradecanoylphorbol-13-acetate (TPA). To characterize the transport of [3H]-digoxin and the metabolism of midazolam i...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Cummins CL,Mangravite LM,Benet LZ

    更新日期:2001-08-01 00:00:00

  • Mechanisms of tumor vascular priming by a nanoparticulate doxorubicin formulation.

    abstract:PURPOSE:Tumor vascular normalization by antiangiogenic agents may increase tumor perfusion but reestablish vascular barrier properties in CNS tumors. Vascular priming via nanoparticulate carriers represents a mechanistically distinct alternative. This study investigated mechanisms by which sterically-stabilized liposom...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Roy Chaudhuri T,Arnold RD,Yang J,Turowski SG,Qu Y,Spernyak JA,Mazurchuk R,Mager DE,Straubinger RM

    更新日期:2012-12-01 00:00:00

  • Structure-transport relationship for the intestinal small-peptide carrier: is the carbonyl group of the peptide bond relevant for transport?

    abstract:PURPOSE:The objective of this study was to determine the influence of the peptide bond with emphasis on the carbonyl group on the interaction with and transport by the intestinal small-peptide carrier. Therefore enalapril, a known substrate for the small-peptide carrier, has been modified to an analogue with a reduced ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Schoenmakers RG,Stehouwer MC,Tukker JJ

    更新日期:1999-01-01 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


    authors: Lestini G,Dumont C,Mentré F

    更新日期:2015-10-01 00:00:00