Abstract：
PURPOSE:The purpose of this work was to determine whether a new modeling methodology using fuzzy logic c an predict skin permeability coefficients that are given compound descriptors that have been proven to affect percutaneous penetration. METHOD:Three fuzzy inference models were developed using subtractive clustering to define natural structures within the data and assign subsequent rules. The numeric parameters describing the rules were refined through the use of an Adaptive Neural Fuzzy Inference System implemented in MatLab. Each model was evaluated using the entire data set. Then predicted outputs were compared to the published experimental data. RESULTS:All databases produced fuzzy inference models that successfully predicted skin permeability coefficients, with correlation coefficients ranging from 0.83 to 0.97. The lowest correlation coefficient resulted from a model using log octanol/water partition coefficient and molecular weight as inputs with two input membership functions evaluated by two fuzzy rules. T he correlation coefficient of 0.97 occurred when log octanol/water partition coefficient and hydrogen bond donor activity were used as inputs with three input membership functions evaluated by three fuzzy rules. CONCLUSIONS:Fuzzy rule-based models are a realistic and promising tool that can be used to successfully model and predict skin permeability coefficients as well as or better than previous algorithms with fewer inputs.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Pannier AK,Brand RM,Jones DDdoi
10.1023/a:1022273115847subject
Has Abstractpub_date
2003-02-01 00:00:00pages
143-8issue
2eissn
0724-8741issn
1573-904Xjournal_volume
20pub_type
杂志文章abstract：:Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018956516640
更新日期：1992-01-01 00:00:00
abstract：:Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) esca...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1012187414126
更新日期：1997-07-01 00:00:00
abstract：PURPOSE:Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02929-2
更新日期：2020-09-28 00:00:00
abstract：PURPOSE:Microphysiological systems (MPS), also known as "organs-on-chips" or "tissue chips," leverage recent advances in cell biology, tissue engineering, and microfabrication to create in vitro models of human organs and tissues. These systems offer promising solutions for modeling human physiology and disease in vitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-019-2742-0
更新日期：2019-12-17 00:00:00
abstract：PURPOSE:To evaluate 26 marketed oncology drugs for time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes. Evaluate TDI-positive drugs for potential to generate reactive intermediates. Assess clinical drug-drug interaction (DDI) risk using static mechanistic models. METHODS:Human liver microsomes and CYP-spe...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0724-6
更新日期：2012-07-01 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：:Chemical enhancers and vehicles were tested for their ability to improve the percutaneous absorption of leuprolide, a nonapeptide (luteinizing hormone releasing hormone analogue; MW 1209.4). In vitro permeabilities in nude mouse, snake, and cadaver skin were evaluated in either Franz diffusion cells or a Bronaugh flow...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015860324161
更新日期：1992-12-01 00:00:00
abstract：PURPOSE:The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate w...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2724-2
更新日期：2020-01-02 00:00:00
abstract：:Monte Carlo simulation technique used to evaluate the effect of the arrangement of concentrations on the efficiency of estimation of population pharmacokinetic parameters in the preclinical setting is described. Although the simulations were restricted to the one compartment model with intravenous bolus input, they pr...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016267811074
更新日期：1995-05-01 00:00:00
abstract：PURPOSE:In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products. METHODS:Different sugars as ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1634-1
更新日期：2015-07-01 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：PURPOSE:SN-38, a potent chemotherapeutic drug, has not been used clinically because of its severe side effects and poor solubility. In this work, we aimed to evaluate the effect of dose and multiple injections of SN-38-loaded polymeric depots on antitumor efficacy and toxicity in vivo. METHODS:Preparation and characte...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2011-4
更新日期：2016-12-01 00:00:00
abstract：PURPOSE:The pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed. METHODS:Betamethasone i...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-004-7681-7
更新日期：2004-12-01 00:00:00
abstract：PURPOSE:The objective of this study was to investigate the possible influence of probenecid on morphine transport across the blood-brain barrier (BBB) in rats. METHODS:Microdialysis probes, calibrated using retrodialysis by drug, were placed into the striatum and jugular vein of seven Sprague-Dawley rats. Morphine was...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1023250900462
更新日期：2003-04-01 00:00:00
abstract：PURPOSE:Indomethacin is well known to be metabolized via O-demethylation and N-deacylation. In this paper we found an enzyme involved in the hydrolysis of amide-linkage of indomethacin and partially characterized it as well as its substrate specificity. METHODS:An indomethacin hydrolyzing enzyme was purified to homoge...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016061614399
更新日期：1996-09-01 00:00:00
abstract：PURPOSE:To compare the ability of alkyl-aryl isothiocyanates (ITCs) to increase the activities of the Phase 2 detoxification enzymes NAD[P]H:quinone acceptor oxidoreductase 1 (NQO1) and glutathione S-transferases (GST) in rat tissues in vivo and in cells in vitro. MATERIALS AND METHODS:Twelve alkyl-aryl ITCs and the f...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9595-2
更新日期：2008-09-01 00:00:00
abstract：:A new magnetic microsphere carrier has been formulated that may localize drugs by both biochemical and physical means. The microspheres, prepared from the polysaccharide chitosan, are designed to bind to anionic glycosaminoglycan receptors on the surface of capillary endothelial cells. The microspheres were formulated...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015978704810
更新日期：1988-05-01 00:00:00
abstract：:The origin of the microheterogeneity of a highly purified antiinflammatory humanized monoclonal antibody prepared in mammalian cell culture has been investigated. This antibody is an IgG directed toward human CD18 (a subunit of leukocyte integrins). When the IgG preparation is subjected to isoelectric focusing, it is ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018912417607
更新日期：1993-11-01 00:00:00
abstract：PURPOSE:The aim was to evaluate fluorescent molecular rotors (DCVJ and CCVJ), which are mainly sensitive to viscosity, for the characterization of polysorbate-containing IgG formulations and compare them to the polarity-sensitive dyes ANS, Bis-ANS and Nile Red. METHODS:IgG formulations with polysorbate 20 or 80 were s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-0020-2
更新日期：2010-02-01 00:00:00
abstract：PURPOSE:Drug transfer into milk is a general concern during lactation. Because data are limited in human subjects, particularly for new drugs, experimental animal models of lactational drug transfer are critical. This study analyzed drug transfer into milk in a mouse model, as well as the contribution of similar and di...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1085-5
更新日期：2013-09-01 00:00:00
abstract：PURPOSE:Interleukin-10 (IL-10) is an anti-inflammatory molecule that has achieved interest as a therapeutic for neuropathic pain. In this work, the potential of plasmid DNA-encoding IL-10 (pDNA-IL-10) slowly released from biodegradable microparticles to provide long-term pain relief in an animal model of neuropathic pa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0077-y
更新日期：2010-05-01 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:We have shown that the three human prostate xenograft tumors, i.e. the androgen-dependent CWR22 tumor, and the androgen-resistant CWR22R and CWR91 tumors, are comparable to patient tumors in their expression of prostate specific antigen, multidrug resistance p-glycoprotein, p53 and Bcl-2 and in their sensitivit...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011921031564
更新日期：1998-11-01 00:00:00
abstract：PURPOSE:To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability. METHODS:A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9852-z
更新日期：2009-06-01 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 characterize factor(s) contained in apical medium of primary cultured rat alveolar epithelial type II cell-like monolayers (RAECM-II) that enhance insulin absorption across alveolar epithelial cells. MATERIALS AND METHODS:Primary rat alveolar epithelial cell monolayers cultured on Transwells in the presence...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9301-9
更新日期：2007-09-01 00:00:00
abstract：PURPOSE:The purpose of this study is to investigate the characteristics of pGlu-L-Dopa-Pro as a prodrug of L-Dopa. METHODS:pGlu-L-Dopa-Pro and L-Dopa-Pro were synthesized using the standard procedures of peptide synthesis. The conversion of pGlu-L-Dopa-Pro to L-Dopa was studied using pyroglutamyl aminopeptidase I and ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016239321494
更新日期：1995-07-01 00:00:00
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
doi：10.1007/s11095-006-9230-z
更新日期：2007-06-01 00:00:00
abstract：:Loracarbef is an oral 1-carba-1-dethiacephalosporin antibiotic structurally related to cefaclor. Like many beta-lactam antibiotics, loracarbef exists in several hydrated crystalline forms. The pH-solubility profile curve for loracarbef monohydrate is U-shaped, resembling those of other zwitterionic cephalosporins. Lor...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018949709797
更新日期：1992-02-01 00:00:00
abstract：:New generation vaccines, particularly those based on recombinant proteins and DNA, are likely to be less reactogenic than traditional vaccines but are also less immunogenic. Therefore, there is an urgent need for the development of new and improved vaccine adjuvants. Adjuvants can be broadly separated into two classes...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1016104910582
更新日期：2002-06-01 00:00:00
