Abstract：
:Animal models are used commonly in various stages of drug discovery and development to aid in the prospective assessment of drug-drug interaction (DDI) potential and the understanding of the underlying mechanism for DDI of a drug candidate. In vivo assessments in an appropriate animal model can be very valuable, when used in combination with in vitro systems, to help verify in vivo relevance of the in vitro animal-based results, and thus substantiate the extrapolation of in vitro human data to clinical outcomes. From a pharmacokinetic standpoint, a key consideration for rational selection of an animal model is based on broad similarities to humans in important physiological and biochemical parameters governing drug absorption, distribution, metabolism or excretion (ADME) processes in question for both the perpetrator and victim drugs. Equally critical are specific in vitro and/or in vivo experiments to demonstrate those similarities, usually both qualitative and quantitative, in the ADME properties/processes under investigation. In this review, theoretical basis and specific examples are presented to illustrate the utility of the animal models in assessing the potential and understanding the mechanisms of DDIs.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Tang C,Prueksaritanont Tdoi
10.1007/s11095-010-0157-zsubject
Has Abstractpub_date
2010-09-01 00:00:00pages
1772-87issue
9eissn
0724-8741issn
1573-904Xjournal_volume
27pub_type
杂志文章,评审abstract：:Various derivatives of the C-terminal amide group in N-protected amino acid and peptide amides were synthesized to assess their suitability as prodrug forms with the aim of protecting the amide or peptide bond against cleavage by alpha-chymotrypsin. Whereas N-acetylation, N-hydroxymethylation, and N-phthalidylation di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015854718903
更新日期：1991-12-01 00:00:00
abstract：:Dihydropyridine ⇄ pyridinium salt-based brain-selective delivery systems were synthesized for the progestins, ethisterone, norethindrone, and norgestrel. After initial lipophilicity and in vitro studies indicated the feasibility of applying these compounds to brain-specific delivery, in vivo distribution studies were ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016359301852
更新日期：1986-10-01 00:00:00
abstract：:Using brine shrimp lethality to direct fractionation, extracts of the bark of Annona bullata Rich. (Annonaceae) have yielded 16 alpha-hydroxy-(-)-kauranoic acid as a bioactive plant constituent. This previously known diterpene showed significant (ED50 8.25 x 10(-2) micrograms/ml) and selective cytotoxicity against A-5...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015819422479
更新日期：1990-04-01 00:00:00
abstract：PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-9009-z
更新日期：2005-01-01 00:00:00
abstract：PURPOSE:To develop a non-viral gene delivery system in the form of an oil-in-water (o/w) lipid emulsion. METHOD:Cationic lipid emulsions were formulated with soybean oil, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as a cationic emulsifier and other co-emulsifiers. The physical characteristics of the l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007553106681
更新日期：2000-03-01 00:00:00
abstract：:The effect of buprenorphine on bremazocine-induced diuresis was tested in the rat to determine the nature of buprenorphine's action at the ϰ opioid receptor. Both morphine-tolerant and naive rats were used to account for possible antidiuretic effects of buprenorphine at the µ site. Separate experiments established tha...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016340106299
更新日期：1985-07-01 00:00:00
abstract：:Excessive production of reactive oxygen species by alveolar macrophages (AMs) in response to inhaled toxic substances is a major cause of oxidative lung injury. Therapeutic approaches designed to protect the lungs from oxidative injury by administering native antioxidant enzymes such as catalase and superoxide dismuta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018976529766
更新日期：1994-08-01 00:00:00
abstract：:The stability of a freeze-dried model protein, ribonuclease A (RNase), was investigated under accelerated storage conditions at 45 degrees C for time periods up to 60 days. Because RNase is a fairly stable molecule around pH 7, lyophilization was performed in phosphate buffers at pH 4.0 or 10.0 to accelerate degradati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015959604616
更新日期：1990-10-01 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：:Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory antagonist of interleukin-1 family of pro-inflammatory cytokines. The broad spectrum anti-inflammatory effects of IL-1Ra have been investigated against various auto-immune diseases such as diabetes mellitus, rheumatoid arthritis. Des...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-013-1118-0
更新日期：2013-11-01 00:00:00
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
doi：10.1023/a:1022282221530
更新日期：2003-01-01 00:00:00
abstract：:A two-step analytic procedure to determine the rate and extent of metabolite production following administration of the parent compound is described. The procedure provides the rate and extent of metabolite production as a function of time by application of the general model independent approach of deconvolution. The ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015951426191
更新日期：1988-06-01 00:00:00
abstract：PURPOSE:We present a smart intradermal interface suitable for skin-attached drug delivery devices. Our solution enables injections or infusions that are less invasive compared to subcutaneous injections and are leakage-free at the location of penetration. METHODS:The intradermal interface is based on a 31-gauge cannul...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0319-z
更新日期：2011-03-01 00:00:00
abstract：PURPOSE:Our previous studies showed that the mRNA level of human organic anion transporter (hOAT) 3 in the kidney was correlated with the rate of elimination of an anionic antibiotic cefazolin. However, the correlation coefficient was not so high. In the present study, therefore, we enrolled more patients to examine wh...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-8383-5
更新日期：2005-12-01 00:00:00
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
doi：10.1023/b:pham.0000033016.36825.2c
更新日期：2004-07-01 00:00:00
abstract：PURPOSE:An integrated ionic mobility-pore model for epidermal iontophoresis is developed from theoretical considerations using both the free volume and pore restriction forms of the model for a range of solute radii (rj) approaching the pore radii (rp) as well as approximation of the pore restriction form for rj/rp < 0...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011907201096
更新日期：1998-10-01 00:00:00
abstract：:Defined size fractions of polyethyleneglycol powder (MW = 10,000) were mixed with defined size fractions of alpha-lactose monohydrate in order to study the effect of compaction as a function of the weight ratios of the two excipients. For a precise control of the compression cycle, tablets were compressed on a Univers...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015864415693
更新日期：1990-02-01 00:00:00
abstract：PURPOSE:Manufacturing processes for polypeptide/protein drugs are designed to ensure robust quality, efficacy and safety. Process differences introduced by follow-on manufacturers may result in changes in quality and clinical outcomes. This study investigated the impact of production methods on the stability and impuri...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02817-9
更新日期：2020-06-08 00:00:00
abstract：PURPOSE:To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells. METHODS:Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scan...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9760-7
更新日期：2009-03-01 00:00:00
abstract：:The interaction between several marker solutes and a polyolefin laminate polymer was studied in several solutions. Solutions studied included mixtures of sodium chloride and dextrose (at concentrations more less typical of i.v. administration solutions) and several actual i.v. products [lactated Ringer's injection, Di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015866420836
更新日期：1991-06-01 00:00:00
abstract：PURPOSE:To study the influence of crystallizing and non-crystallizing cosolutes on the crystallization behavior of trehalose in frozen solutions and to monitor the phase behavior of trehalose dihydrate and mannitol hemihydrate during drying. METHODS:Trehalose (a lyoprotectant) and mannitol (a bulking agent) are widely...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0221-8
更新日期：2010-11-01 00:00:00
abstract：PURPOSE:Following extracellular drug clearance, we analyzed the rate of doxorubicin efflux from the nucleus of three human leukemic cells (K562, Molt4 and CCRF-CEM) and related it to their differential sensitivity to this drug, after a short drug pulse. RESULTS:For many pulse-chase regimes, K562 cell viability was lea...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9369-2
更新日期：2007-11-01 00:00:00
abstract：PURPOSE:Monoamine oxidases (MAOs) are non-CYP enzymes that contribute to systemic elimination of therapeutic agents, and localized on mitochondrial membranes. The aim of the present study was to validate quantitative estimation of metabolic clearance of MAO substrate drugs using human liver microsomes (HLMs). METHODS:...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2140-4
更新日期：2017-06-01 00:00:00
abstract：PURPOSE:The aim of this study was to identify the dominant factors affecting the stability of nanoemulsions, using artificial neural networks (ANNs). METHODS:A nanoemulsion preparation of budesonide containing polysorbate 80, ethanol, medium chain triglycerides and saline solution was designed, and the particle size o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0004-2
更新日期：2010-01-01 00:00:00
abstract：PURPOSE:Iontophoresis was employed for enhancing the transdermal delivery of acyclovir through nude mouse skin in vitro, with the aim of understanding the mechanisms responsible for drug transport, in order to properly set the conditions of therapeutical application. METHODS:Experiments were done in horizontal diffusi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016284815501
更新日期：1995-11-01 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：PURPOSE:A rapid immune response is required to prevent death from Anthrax, caused by Bacillus anthracis. METHOD:We formulated a vaccine carrier comprised of acetalated dextran microparticles encapsulating recombinant protective antigen (rPA) and resiquimod (a toll-like receptor 7/8 agonist). RESULTS:We were able to p...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-0975-x
更新日期：2013-05-01 00:00:00
abstract：PURPOSE:To develop a method for drawing statistical inferences from differences between multiple experimental pair distribution function (PDF) transforms of powder X-ray diffraction (PXRD) data. METHODS:The appropriate treatment of initial PXRD error estimates using traditional error propagation algorithms was tested ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0259-7
更新日期：2010-12-01 00:00:00
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
doi：10.1023/A:1016301919928
更新日期：1985-11-01 00:00:00
abstract：PURPOSE:Paclitaxel is active and widely used to treat multiple types of solid tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol (C/E) as the solubilizers. Other formulations including nanoparticles have been introduced. This study evaluated the effects of nanoparticle formulation of pacli...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-4581-4
更新日期：2005-06-01 00:00:00
