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 (positive, negative or no effect) on AUC of 92 entries and physicochemical parameters, including clinical doses used in the food effect study, solubility (pH 7), dose number (dose/solubility at pH 7), calculated Log D (pH 7), polar surface area, total surface area, percent polar surface area, number of hydrogen bond donor, number of hydrogen bond acceptors, and maximum absorbable dose (MAD). RESULTS:For compounds with MAD >or= clinical dose, the food effect can be predicted from the dose number category and Log D category, while for compounds with MAD < clinical dose, the food effect can be predicted from the dose number category alone. With cross validation, 74 out of 92 entries (80%) were predicted into the correct category. The correct predictions were 97, 79 and 68% for compounds with positive, negative and no food effect, respectively. CONCLUSIONS:A logistic regression model based on dose, solubility, and permeability of compounds is developed to predict the food effect on AUC. Statistically, solubilization effect of food primarily accounted for the positive food effect on absorption while interference of food with absorption caused negative effect on absorption of compounds that are highly hydrophilic and probably with narrow window of absorption.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Gu CH,Li H,Levons J,Lentz K,Gandhi RB,Raghavan K,Smith RLdoi
10.1007/s11095-007-9236-1subject
Has Abstractpub_date
2007-06-01 00:00:00pages
1118-30issue
6eissn
0724-8741issn
1573-904Xjournal_volume
24pub_type
杂志文章abstract：PURPOSE:The aim of this study was to develop a labile sphingosine-based liposome for intramuscular gene delivery. METHODS:Sphingosine-based liposomes were formulated in a range of solutions with phosphatidylcholine, then were associated to DNA. The physico-chemical characteristics of the sphingosine/EPC liposomes and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1019894008885
更新日期：2002-08-01 00:00:00
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
更新日期：2003-11-01 00:00:00
abstract：:The electrochemical properties of human cadaver skin were studied in a diffusion cell with impedance spectroscopy as a function of time in the absence and presence of penetration enhancers dodecyl N,N-dimethylamino acetate and Azone. An improved electrochemical model of skin is presented, and combining the novel model...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018984121415
更新日期：1993-03-01 00:00:00
abstract：PURPOSE:Type I collagen accumulates during liver fibrosis primarily because α-complex protein-2 (αCP(2)), encoded by the poly(rC) binding protein 2 (PCBP2) gene, binds to the 3' end of the collagen mRNA and increases its half-life. This study aimed to reverse the pro-fibrogenic effect of alcohol on hepatic stellate cel...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0475-9
更新日期：2011-12-01 00:00:00
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
doi：10.1007/s11095-005-6037-2
更新日期：2005-07-01 00:00:00
abstract：PURPOSE:This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA). METHODS:The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared un...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-9395-x
更新日期：2006-03-01 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 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
doi：10.1007/s11095-012-0815-4
更新日期：2012-11-01 00:00:00
abstract：PURPOSE:To determine the different conformations of the acyloxyalkoxy-linked cyclic prodrug 1 of the model hexapeptide 2 in solution and to investigate the relationship between these solution conformations and the cellular permeability characteristics of this prodrug. METHODS:Two-dimensional Homonuclear Hartmann-Hahn ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016484522113
更新日期：1996-11-01 00:00:00
abstract：PURPOSE:The purpose of this research was to evaluate the effect of ultrasound on mass transport across fetal membrane for direct fetal drug delivery and sensing of the amniotic fluid in a noninvasive manner. METHODS:Post-delivery human fetal membranes (chorioamnion) were used for in vitro experiments, in which the eff...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1470-8
更新日期：2015-02-01 00:00:00
abstract：PURPOSE:1. The assessment of the role of hair follicles and sweat glands in skin resistance and percutaneous iontophoretic flux of 9-desglycinamide, 8-arginine vasopressin (DGAVP) by comparing two skin species: human stratum corneum which contained hair follicles, sweat and sebaceous glands, and shed snake skin which l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016243706415
更新日期：1995-10-01 00:00:00
abstract：PURPOSE:Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. MET...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1887-3
更新日期：2016-06-01 00:00:00
abstract：PURPOSE:Recombinant human platelet glycoprotein Ibalpha-immunoglobulin G1 chimeric proteins (GPIbalpha-Ig) have varying levels of anti-thrombotic activities based on their ability to compete for platelet mediated adhesion to von Willebrand Factor (vWF). Valine substituted GPIbalpha-Ig chimeras, at certain position, inc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9018-1
更新日期：2006-08-01 00:00:00
abstract：:A 1H-NMR spectroscopic method for the determination of the optical purity of threo-methylphenidate hydrochloride is presented. Complexation of the free-base form of the substrate with a chiral Eu(III) shift reagent resulted in two distinct enantiomeric ester methyl proton signals of utility for quantitative work. The ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015815605583
更新日期：1990-07-01 00:00:00
abstract：PURPOSE:Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-a...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1660-z
更新日期：2015-08-01 00:00:00
abstract：PURPOSE:To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides. METHODS:GR was administered...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016033124819
更新日期：1996-12-01 00:00:00
abstract：PURPOSE:Levofloxacin, a quinolone antibacterial drug, is a zwitterion at physiological pH. We examined the effect of cationic and anionic drugs on renal excretion of levofloxacin by means of in vivo clearance to characterize the mechanisms of renal excretion of this drug. METHODS:In vivo clearance was studied in male ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012111902798
更新日期：1997-04-01 00:00:00
abstract：PURPOSE:The effects of liposomes on nitric oxide (NO) production from mouse peritoneal macrophages following intraperitoneal injection of liposomes were investigated. METHODS:Mouse peritoneal macrophages were collected following intraperitoneal injection of liposomes and cultured with and without lipopolysaccharide (L...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016034303012
更新日期：1996-09-01 00:00:00
abstract：PURPOSE:The purpose of the current study is to evaluate the solubility advantage offered by celecoxib (CEL) amorphous systems and to characterize and correlate the physical and thermodynamic properties of CEL and its amorphous molecular dispersions containing poly(vinylpyrrolidone) (PVP). METHODS:The measurement of cr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000045226.42859.b8
更新日期：2004-10-01 00:00:00
abstract：PURPOSE:The in-situ particle size of delavirdine mesylate in dry mix and tablets was determined. METHODS:Optical microscopy and fluorescence microscopy combined with image analysis were used for qualitative and quantitative measurements. RESULTS:Using optical microscopy, it was demonstrated qualitatively that fragmen...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018875130152
更新日期：1999-04-01 00:00:00
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
doi：10.1007/s11095-011-0540-4
更新日期：2012-01-01 00:00:00
abstract：PURPOSE:Evista (raloxifene HCl) is a nonsteroidal selective estrogen receptor modulator that displays estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects on the breast and endometrium. The potential for drug-drug interaction between raloxifene and warfarin was assessed in 15 healthy po...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1010904815275
更新日期：2001-07-01 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:To study the influence of solid form on the behavior of the salt siramesine hydrochloride in aqueous environments. METHODS:The solubilities and dissolution rates of siramesine hydrochloride anhydrate and monohydrate were determined at pH 3.4 and 6.4, and precipitates were examined by X-ray powder diffraction. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9783-0
更新日期：2009-04-01 00:00:00
abstract：:The transepithelial transport of arginine vasopressin (AVP) across cultured rat alveolar epithelial cell monolayers was studied. At 0.1 nM donor [125I]AVP, the radiolabel flux measured in the apical-to-basolateral (AB) direction was about 10 times greater than that in the reverse (BA) direction. HPLC analyses of the b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018918022865
更新日期：1994-11-01 00:00:00
abstract：PURPOSE:The development of a physiologically based absorption model for orally administered drugs in rats is described. METHODS:Unlike other models that use a multicompartmental approach, the GI tract is modeled as a continuous tube with spatially varying properties. The mass transport through the intestinal lumen is ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000003373.72652.c0
更新日期：2003-11-01 00:00:00
abstract：PURPOSE:To investigate if gamma-Hydroxybutyrate (GHB) tolerance is mediated by alterations in GHB systemic pharmacokinetics, transport (blood brain barrier (BBB) and neuronal) or membrane fluidity. MATERIALS AND METHODS:GHB tolerance in rats was attained by repeated GHB administration (5.31 mmol/kg, s.c., QD for 5 day...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9066-6
更新日期：2006-09-01 00:00:00
abstract：PURPOSE:Covalent binding between N-acetyl-L-cysteine (NAC) and albumin was evaluated kinetically by conducting in vitro experiments. METHOD:After 14C-NAC was incubated with human or rat serum, the solution was analyzed by anion-exchange HPLC. The albumin-bound 14C-NAC was quantified by measuring the radioactivity in t...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1020749211745
更新日期：2002-11-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate the depth-dependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleoti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1965-6
更新日期：2016-09-01 00:00:00
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
doi：10.1007/s11095-012-0823-4
更新日期：2012-12-01 00:00:00
