Abstract：
PURPOSE:Since the absorption of ceftriaxone (CTO) in the intestine is restricted by its natural physiological characteristics, we developed a series of small synthetic compounds derived from bile acids to promote the absorption of CTO in the gastrointestinal tract. METHODS:Several bile acid derivatives were screened by measuring water solubility and partition coefficient of their complexes with CTO. The pharmacokinetic parameters of the selected CTO/HDCK ionic complex in monkeys were evaluated. The absorption pathway of CTO/HDCK complex was evaluated using Caco-2 cells and MDCK cells transfected with ASBT gene. RESULTS:HDCK enhanced the apparent membrane permeability of CTO 5.8-fold in the parallel artificial membrane permeability assay model. CTO/HDCK complex permeated Caco-2 cell via transcellular pathway, and interaction of the HDCK complex with ASBT was important to enhance uptake. When CTO/HDCK (equivalent to 50 mg/kg of ceftriaxone) formulated with lactose, poloxamer 407 and Labrasol was orally administered to monkeys, its maximum plasma concentration was 19.5 ± 1.8 μg/ml and oral bioavailability 28.5 ± 3.1%. CONCLUSIONS:The CTO/HDCK formulation could enhance oral bioavailability of CTO in non-human primates. This oral formulation could be an alternative to injectable CTO with enhanced clinical effects.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Jeon OC,Hwang SR,Al-Hilal TA,Park JW,Moon HT,Lee S,Park JH,Byun Ydoi
10.1007/s11095-012-0932-0subject
Has Abstractpub_date
2013-04-01 00:00:00pages
959-67issue
4eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
杂志文章abstract：PURPOSE:Percutaneous absorption assays of molecules for pharmaceutical and cosmetology purposes are important to determine the bioavailability of new compounds, once topically applied. The current method of choice is to measure the rate of diffusion through excised human skin using a diffusion cell. This method however...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1654-x
更新日期：2015-08-01 00:00:00
abstract：:We studied the effects of two verapamil analogs, anipamil and ronipamil, in traumatic shock. Noble-Collip drum trauma produced a shock state characterized by an eight-fold increase in plasma cathepsin D activity, a 13-fold increase in the rate of plasma myocardial depressant factor (MDF) accumulation, and a survival t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016363316777
更新日期：1985-05-01 00:00:00
abstract：PURPOSE:The aim of the study is to determine the effect of experimental parameters on microinfusion through hollow microneedles into skin to optimize drug delivery protocols and identify rate-limiting barriers to flow. METHODS:Glass microneedles were inserted to a depth of 720-1080 microm into human cadaver skin to mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8498-8
更新日期：2006-01-01 00:00:00
abstract：:Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (C(max)) and time to peak concentration (T(max)), although these parameters are indirect measures of absorption rate. Re...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-011-0421-x
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:To develop a novel bioadhesive polymer that protects peptide drugs from luminal degradation by aminopeptidase N and to evaluate the system in vitro on porcine mucosa. METHODS:EDTA was covalently bound to chitosan in order to combine the bioadhesive properties of the polymer with the well known capacity of EDTA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012108118670
更新日期：1997-07-01 00:00:00
abstract：PURPOSE:This study was conducted to assess the pharmacokinetics and pharmacodynamics of 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (NOS). METHODS:Male Sprague-Dawley rats were equipped with peritoneal/ venous cannulae and a microdialysis probe in the hippocampal cortex. Rats receiv...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013042817281
更新日期：2001-11-01 00:00:00
abstract：PURPOSE:A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS:Human growth ho...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018834305079
更新日期：1999-06-01 00:00:00
abstract：PURPOSE:The purpose of the present study was to explore the involvement of indoxyl sulfate (IS) in nephrotoxicity and central nervous system (CNS) toxicity in cisplatin (CDDP)-treated rats. MATERIALS AND METHODS:Renal function was evaluated by serum creatinine and BUN levels. The IS levels in the serum, brain and kidn...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9183-2
更新日期：2007-04-01 00:00:00
abstract：PURPOSE:To develop a statistical model for predicting effect of food on the extent of absorption (area under the curve of time-plasma concentration profile, AUC) of drugs based on physicochemical properties. MATERIALS AND METHODS:Logistic regression was applied to establish the relationship between the effect of food ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9236-1
更新日期：2007-06-01 00:00:00
abstract：PURPOSE:Non-small cell lung cancer is the leading cause of cancer related deaths globally. Considering the side effects and diminishing chemosensitivity to chemotherapy, novel treatment approaches are sought. Hence, we aim to develop a liposomal co-delivery system of pDNA expressing shRNA against PFKFB3 (pshPFKFB3) and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2244-x
更新日期：2017-11-01 00:00:00
abstract：:Physicochemical effects caused by intestinal fluids on drugs in the gastrointestinal (GI) tract can be a contributing factor in food induced changes in bioavailability. To identify physicochemical properties of gemfibrozil that may be altered by endogenous and dietary lipids, in vitro studies were conducted in model s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018967401000
更新日期：1994-12-01 00:00:00
abstract：:The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-017-2223-2
更新日期：2017-11-01 00:00:00
abstract：PURPOSE:To produce and characterize a nonviral ultrasound-controlled release system of plasmid DNA (pDNA) encapsulated in gas-filled poly(D,L-lactide-co-glycolide) microparticles (PLGA-MPs). METHODS:Different cationic polymers were used to form pDNA/polymer complexes to enhance the stability of pDNA during micropartic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014430631844
更新日期：2002-03-01 00:00:00
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
更新日期：1989-05-01 00:00:00
abstract：PURPOSE:To investigate the relationship between mean dissolution time (MDT) and dose/solubility ratio (q) using the diffusion layer model. METHODS:Using the classic Noyes-Whitney equation and considering a finite dose, we derived an expression for MDT as a function of q under various conditions. q was expressed as a d...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022652004114
更新日期：2003-03-01 00:00:00
abstract：PURPOSE:To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer(®)) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes. METHODS:Spray dried mannitol (SDM) partic...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1132-2
更新日期：2014-01-01 00:00:00
abstract：PURPOSE:Phase II metabolism involves the conjugation of a polar moiety, such as sulfate or glucuronic acid, to a (relatively) nonpolar xenobiotic. Although it might be expected that such conjugates may exhibit amphiphilic character (e.g., surface activity and potential to form micelles), no detailed study of the micell...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1022672608657
更新日期：2003-03-01 00:00:00
abstract：PURPOSE:To describe a computational tool to calculate molecular descriptors of potential application in ADME virtual screening of antitumor Pt(II) drug candidates. METHODS:The multistep computational procedure consists in (a) building and optimization (PM3) of the 3D structures of the investigated complexes, (b) param...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0317-1
更新日期：2011-03-01 00:00:00
abstract：PURPOSE:The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. METHODS:The anti-acne agent, adapalene, was encapsulated in acid-responsive polyme...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1398-z
更新日期：2014-11-01 00:00:00
abstract：PURPOSE:Predicting human skin permeability of chemical compounds accurately and efficiently is useful for developing dermatological medicines and cosmetics. However, previous work have two problems; 1) quality of databases used, and 2) methods for prediction models. In this paper, we attempt to solve these two problems...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1629-y
更新日期：2015-07-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015828027060
更新日期：1992-04-01 00:00:00
abstract：PURPOSE:Supramolecular Biovectors (SMBV) consist of cross-linked cationic nanoparticles surrounded by a lipid membrane. The purpose was to study the structure of the lipid membrane and to characterise its interaction with the nanoparticles in order to differentiate SMBV from other polymer/lipid associations. METHODS:T...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007504124603
更新日期：2000-07-01 00:00:00
abstract：:The effects of skin storage, skin preparation, skin pretreatment with a penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4 degrees C...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015822431178
更新日期：1992-03-01 00:00:00
abstract：PURPOSE:β-Hydroxy-β-methylbutyrate (HMB), a nutritional supplement, elicits anabolic activity in muscle. Here we investigated the mechanism of HMB uptake in muscle cells. METHODS:Murine muscle cells (C2C12) and human mammary epithelial cells (MCF7) were used for uptake. As HMB is a monocarboxylate, focus was on monoca...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2626-3
更新日期：2019-04-17 00:00:00
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
doi：10.1023/a:1011048831698
更新日期：2001-06-01 00:00:00
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
doi：10.1023/a:1018902120023
更新日期：1993-04-01 00:00:00
abstract：PURPOSE:The purpose of this study was to investigate the delivery of itraconazole (ITZ) particles to a murine lung model by nebulization. METHODS:Three ITZ formulations were prepared and characterized in the dry state using contact angle, dissolution, X-ray powder diffraction, scanning electron microscopy, and Brunaue...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9904-6
更新日期：2006-05-01 00:00:00
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
doi：10.1023/a:1016205520044
更新日期：1995-11-01 00:00:00
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
更新日期：1993-07-01 00:00:00
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
doi：10.1023/a:1011907920641
更新日期：1999-02-01 00:00:00
