Pharmacokinetics/Pharmacodynamics Evaluation of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli In Vitro and In Vivo in a Murine Thigh Infection Model.


PURPOSE:Although flomoxef (FMOX) has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of FMOX against ESBL-producing E. coli is unclear. The aim of this study was to determine the PK/PD index of FMOX against ESBL-producing E. coli. METHODS:In vitro time-kill curve studies and in vivo PK/PD experiments were carried out. RESULTS:Time-kill curves exhibited a unique bactericidal activity: time-dependent activity at low concentrations and concentration-dependent activity at high concentrations. In neutropenic murine thigh infection experiments, the antibacterial activity of FMOX correlated with the time that the free drug concentration remaining above the minimum inhibitory concentration (MIC) (fT>MIC) and the ratio of the area under the free drug concentration-time curve for a 24 h period to the MIC (fAUC24/MIC). However, the burden of ESBL producing E. coli significantly reduced when the time intervals for administration were shorter among three dosage regimens with same magnitude of fAUC24/MIC, indicating that fT>MIC is significant PK/PD index. The target value of fT>MIC for 1 log10 kill reduction was 35.1%. CONCLUSIONS:fT>MIC is the most significant PK/PD index of FMOX against ESBL-producing E. coli and its target value is ≥ 40%.


Pharm Res


Pharmaceutical research


Tashiro S,Hayashi M,Takemura W,Igarashi Y,Liu X,Mizukami Y,Kojima N,Enoki Y,Taguchi K,Yokoyama Y,Nakamura T,Matsumoto K




Has Abstract


2021-01-06 00:00:00








  • Pharmacokinetics of recombinant human interferon-beta ser in healthy volunteers and its effect on serum neopterin.

    abstract::The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcuta...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Chiang J,Gloff CA,Yoshizawa CN,Williams GJ

    更新日期:1993-04-01 00:00:00

  • Bioadhesion of lectin-latex conjugates to rat intestinal mucosa.

    abstract:PURPOSE:The specific interactions between three lectin-latex conjugates and different structures of rat intestinal mucosa have been studied ex vivo. METHODS:These systems were prepared by covalent coupling of different ligands, i.e., tomato lectin (TL), asparagus pea lectin (AL), mycoplasma gallisepticum lectin (ML), ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Irache JM,Durrer C,Duchêne D,Ponchel G

    更新日期:1996-11-01 00:00:00

  • Curcumin Delivery by Poly(Lactide)-Based Co-Polymeric Micelles: An In Vitro Anticancer Study.

    abstract:PURPOSE:This work describes the synthesis of block co-polymeric micelles, methoxy-poly(ethylene glycol)-poly(D,L-lactide) (mPEG-PLA) to encapsulate Curcumin (CUR), thereby improving the dispersibility and chemical stability of curcumin, prolonging its cellular uptake and enhancing its bioavailability. METHODS:CUR-mPEG...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kumari P,Swami MO,Nadipalli SK,Myneni S,Ghosh B,Biswas S

    更新日期:2016-04-01 00:00:00

  • Correction to: A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice.

    abstract::One of the authors has his name incorrectly indexed in PubMed and SpringerLink as "Laird Forrest M" (last name "Laird Forrest"). His name should index as "Forrest M. Laird" with last name as "Forrest". ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,已发布勘误


    authors: Varkhede N,Patel N,Chang W,Ruterbories K,Forrest ML

    更新日期:2018-07-25 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

  • Elucidating the role of dose in the biopharmaceutics classification of drugs: the concepts of critical dose, effective in vivo solubility, and dose-dependent BCS.

    abstract:PURPOSE:To develop a dose dependent version of BCS and identify a critical dose after which the amount absorbed is independent from the dose. METHODS:We utilized a mathematical model of drug absorption in order to produce simulations of the fraction of dose absorbed (F) and the amount absorbed as function of the dose ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Charkoftaki G,Dokoumetzidis A,Valsami G,Macheras P

    更新日期:2012-11-01 00:00:00

  • Cellular handling of a dexamethasone-anti-E-selectin immunoconjugate by activated endothelial cells: comparison with free dexamethasone.

    abstract:PURPOSE:For selective inhibition of endothelial cell activation in chronic inflammation, we have developed a dexamethasone-anti-E-selectin immunoconjugate. The present study was performed to evaluate the cellular handling of this immunoconjugate by activated primary endothelial cells and to compare its drug delivery ca...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kok RJ,Everts M,Asgeirsdóttir SA,Meijer DK,Molema G

    更新日期:2002-11-01 00:00:00

  • Formulation and performance of danazol nano-crystalline suspensions and spray dried powders.

    abstract:PURPOSE:This study focuses on the formulation optimization, in vitro and in vivo performance of differently sized nano-crystalline liquid suspensions and spray-dried powders of a poorly soluble BCS class II compound i.e. Danazol. METHODS:A DoE approach was utilized to optimize stabilizer concentration and formulate da...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kumar S,Jog R,Shen J,Zolnik B,Sadrieh N,Burgess DJ

    更新日期:2015-05-01 00:00:00

  • High variability in drug pharmacokinetics complicates determination of bioequivalence: experience with verapamil.

    abstract:PURPOSE:For the assessment of bioequivalence it is assumed that drug clearance in each subject on each of the study days is the same and any observed differences in AUC and/or Cmax between a brand and generic formulation are due to differences in bioavailability. We hypothesized that this assumption was invalid for hig...

    journal_title:Pharmaceutical research

    pub_type: 临床试验,杂志文章


    authors: Tsang YC,Pop R,Gordon P,Hems J,Spino M

    更新日期:1996-06-01 00:00:00

  • Comparative evaluation of ibuprofen/beta-cyclodextrin complexes obtained by supercritical carbon dioxide and other conventional methods.

    abstract:PURPOSE:The preparation of drug/cyclodextrin complexes is a suitable method to improve the dissolution of poor soluble drugs. The efficacy of the Controlled Particle Deposition (CPD) as a new developed method to prepare these complexes in a single stage process using supercritical carbon dioxide is therefore compared w...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Hussein K,Türk M,Wahl MA

    更新日期:2007-03-01 00:00:00

  • Reducing the Visibility of the Vector/DNA Nanocomplexes to the Immune System by Elastin-Like Peptides.

    abstract:PURPOSE:One of the major hurdles facing nanomedicines is the antibody production against nanoparticles that subsequently results in their opsonization and clearance by macrophages. The objective of this research was to examine and identify the sequence of a low-immunogenic peptide based on recombinant elastin-like poly...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Nouri FS,Wang X,Chen X,Hatefi A

    更新日期:2015-09-01 00:00:00

  • Transport characteristics of peptidomimetics. Effect of the pyrrolinone bioisostere on transport across Caco-2 cell monolayers.

    abstract:PURPOSE:To compare the permeation characteristics of amide bond-containing HIV-1 protease inhibitors and their pyrrolinone-containing counterparts across Caco-2 cell monolayers, a model of the intestinal mucosa. METHODS:Transepithelial transport and cellular uptake of three pairs of amide bond-containing and pyrrolino...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sudoh M,Pauletti GM,Yao W,Moser W,Yokoyama A,Pasternak A,Sprengeler PA,Smith AB 3rd,Hirschmann R,Borchardt RT

    更新日期:1998-05-01 00:00:00

  • Messenger RNA expression of transporter and ion channel genes in undifferentiated and differentiated Caco-2 cells compared to human intestines.

    abstract:PURPOSE:The purpose of this work was to study the influence of cell differentiation on the mRNA expression of transporters and channels in Caco-2 cells and to assess Caco-2 cells as a model for carrier-mediated drug transport in the intestines. METHOD:Gene mRNA expression was measured using a custom-designed microarra...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Anderle P,Rakhmanova V,Woodford K,Zerangue N,Sadée W

    更新日期:2003-01-01 00:00:00

  • Cocrystal formation during cogrinding and storage is mediated by amorphous phase.

    abstract:PURPOSE:The purpose of this work was to investigate the mechanisms of cocrystal formation during cogrinding and storage of solid reactants, and to establish the effects of water by cogrinding with hydrated form of reactants and varying RH conditions during storage. METHODS:The hydrogen bonded 1:1 carbamazepine-sacchar...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Jayasankar A,Somwangthanaroj A,Shao ZJ,Rodríguez-Hornedo N

    更新日期:2006-10-01 00:00:00

  • Stereoselective metabolism of bupropion by cytochrome P4502B6 (CYP2B6) and human liver microsomes.

    abstract:PURPOSE:Hydroxylation of the antidepressant and smoking deterrent drug bupropion is a clinically important bioactivation and elimination pathway. Bupropion hydroxylation is catalyzed selectively by cytochrome P4502B6 (CYP2B6). CYP2B6-catalyzed bupropion hydroxylation has been used as an in vitro and in vivo phenotypic ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Coles R,Kharasch ED

    更新日期:2008-06-01 00:00:00

  • Graphene oxide - gelatin nanohybrids as functional tools for enhanced Carboplatin activity in neuroblastoma cells.

    abstract:PURPOSE:Preparation of Nanographene oxide (NGO) - Gelatin hybrids for efficient treatment of Neuroblastoma. METHODS:Nanohybrids were prepared via non-covalent interactions. Spectroscopic tools have been used to discriminate the chemical states of NGO prior and after gelatin coating, with UV visible spectroscopy reveal...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Makharza S,Vittorio O,Cirillo G,Oswald S,Hinde E,Kavallaris M,Büchner B,Mertig M,Hampel S

    更新日期:2015-06-01 00:00:00

  • Effects of solute characteristics and concentration on a lyotropic liquid crystal: solute-induced phase change.

    abstract::We investigated the effects of increased concentrations of the solutes, salicylic acid, benzoic acid, and o-, m-, and p-methoxy benzoic acids, on the anisotropic properties of a liquid crystal solvent. The lamellar liquid crystal was composed of 37% polyoxyethylene (20) isohexadecyl ether in aqueous buffer of pH 1. Ph...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Ibrahim HG,Sallam ES,Takieddin M,Habboub M

    更新日期:1993-05-01 00:00:00

  • Hyaluronan oligomers-HPMA copolymer conjugates for targeting paclitaxel to CD44-overexpressing ovarian carcinoma.

    abstract:PURPOSE:To evaluate the effect of the size of low molecular weight hyaluronan (LMW-HA) oligomers on the targeting ability of the HA-containing copolymers to the CD44-overexpressing cells for delivering Paclitaxel (PTX) to ovarian cancer. METHODS:LMW-HA oligosaccharides of 4, 6, 8, 10, 12 and 14 sugar residues were att...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Journo-Gershfeld G,Kapp D,Shamay Y,Kopeček J,David A

    更新日期:2012-04-01 00:00:00

  • The Impact of Inadequate Temperature Storage Conditions on Aggregate and Particle Formation in Drugs Containing Tumor Necrosis Factor-Alpha Inhibitors.

    abstract:PURPOSE:To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS:TNF-α inhibitors in their o...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Vlieland ND,Nejadnik MR,Gardarsdottir H,Romeijn S,Sediq AS,Bouvy ML,Egberts ACG,van den Bemt BJF,Jiskoot W

    更新日期:2018-02-05 00:00:00

  • Crystalline form information from multiwell plate salt screening by use of Raman microscopy.

    abstract:PURPOSE:The purpose of this study was to establish a useful methodology, possibly providing information on the stoichiometry of pharmaceutical drug salts obtained from salt screening by using a multiwell plate and a Raman microscope. METHODS:Tamoxifen salt screening was conducted with monobasic and polybasic acids on ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kojima T,Onoue S,Murase N,Katoh F,Mano T,Matsuda Y

    更新日期:2006-04-01 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


    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

  • Population Pharmacokinetics, Efficacy Exposure-response Analysis, and Model-based Meta-analysis of Fenebrutinib in Subjects with Rheumatoid Arthritis [corrected].

    abstract:PURPOSE:Fenebrutinib (GDC-0853), a Bruton's tyrosine kinase (BTK) inhibitor was investigated in a Phase 2 clinical trial in patients with rheumatoid arthritis (RA). Our aim was to apply a model-informed drug development (MIDD) approach to examine the totality of available clinical efficacy data. METHODS:Population pha...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Chan P,Yu J,Chinn L,Prohn M,Huisman J,Matzuka B,Hanley W,Tuckwell K,Quartino A

    更新日期:2020-01-06 00:00:00

  • Solid lipid nanoparticles as delivery systems for bromocriptine.

    abstract:PURPOSE:The present investigation describes a formulative study for the development of innovative drug delivery systems for bromocriptine. METHODS:Solid lipid nanoparticles (SLN) based on different lipidic components have been produced and characterized. Morphology and dimensional distribution have been investigated b...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Esposito E,Fantin M,Marti M,Drechsler M,Paccamiccio L,Mariani P,Sivieri E,Lain F,Menegatti E,Morari M,Cortesi R

    更新日期:2008-07-01 00:00:00

  • Production of ultrafine sumatriptan succinate particles for pulmonary delivery.

    abstract:PURPOSE:Drug particle physical properties are critical for the efficiency of a drug delivered to the lung. The purpose of this study was to produce ultrafine sumatriptan succinate particles for inhalation. METHODS:Sumatriptan succinate particles were produced via reactive precipitation without any surfactants. Several...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Yang ZY,Le Y,Hu TT,Shen Z,Chen JF,Yun J

    更新日期:2008-09-01 00:00:00

  • Direct observation of single particle electrostatic charging by atomic force microscopy.

    abstract:PURPOSE:To show that atomic force microscopy (AFM) can be used to directly study the electrostatic charging and dissipation of single pharmaceutical particles. MATERIALS AND METHODS:Particles of lactose attached to AFM cantilevers were charged on a glass surface at a relative humidity (RH) of 0.1%. By recording force-...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Bunker MJ,Davies MC,James MB,Roberts CJ

    更新日期:2007-06-01 00:00:00

  • A fractal approach to heterogeneous drug distribution: calcium pharmacokinetics.

    abstract:PURPOSE:To point out the importance of heterogeneity in drug distribution processes and develop a noncompartmental approach for the description of the distribution of drug in the body. METHODS:A dichotomous branching network of vessels for the arterial tree connected to a similar venous network was used to describe th...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Macheras P

    更新日期:1996-05-01 00:00:00

  • Interconversion pharmacokinetics of simvastatin and its hydroxy acid in dogs: effects of gemfibrozil.

    abstract:PURPOSE:To characterize the pharmacokinetics of simvastatin (SV) and simvastatin acid (SVA), a lactone-acid pair known to undergo reversible metabolism, and to better understand mechanisms underlying pharmacokinetic interactions observed between SV and gemfibrozil. METHODS:Pharmacokinetic studies were conducted after ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Prueksaritanont T,Qiu Y,Mu L,Michel K,Brunner J,Richards KM,Lin JH

    更新日期:2005-07-01 00:00:00

  • Effect of some penetration enhancers on epithelial membrane lipid domains: evidence from fluorescence spectroscopy studies.

    abstract::The effect of the penetration enhancers Azone, oleic acid, 1-dodecanol, dodecyl N,N-dimethylaminoacetate (DDAA), and dodecyl N,N-dimethylaminoisopropionate (DDAIP) on epithelial membrane lipids was examined using human buccal cell membranes as a model for epithelial lipid bilayer. Buccal epithelial cells (BEC) were la...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Turunen TM,Urtti A,Paronen P,Audus KL,Rytting JH

    更新日期:1994-02-01 00:00:00

  • Manufacture and properties of erythromycin beads containing neutron-activated erbium-171.

    abstract::To evaluate the effects of a neutron activation radiolabeling technique on an enteric-coated multiparticulate formulation of erythromycin, test quantities were produced under industrial pilot scale conditions. The pellets contained the stable isotope erbium oxide (Er-170), which was later converted by neutron activati...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Parr AF,Digenis GA,Sandefer EP,Ghebre-Sellassie I,Iyer U,Nesbitt RU,Scheinthal BM

    更新日期:1990-03-01 00:00:00

  • Predicting skin permeability.

    abstract::Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Potts RO,Guy RH

    更新日期:1992-05-01 00:00:00