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 predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physiocochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an "aqueous-polar (pore) pathway" across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger-than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to greater than 750, and log Koct ranging from -3 to +6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Potts RO,Guy RHdoi
10.1023/a:1015810312465subject
Has Abstractpub_date
1992-05-01 00:00:00pages
663-9issue
5eissn
0724-8741issn
1573-904Xjournal_volume
9pub_type
杂志文章abstract：PURPOSE:The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. METHODS:Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately follo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7677-y
更新日期：2005-11-01 00:00:00
abstract：PURPOSE:The heats of reaction between the enantiomers and racemates of ibuprofen and naproxen and human serum albumin (HSA) are to be measured with and without the addition of octanoic acid. The effects of octanoic acid on the free energies of interaction between the drugs and HSA is to be determined and compared to th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016066325476
更新日期：1996-01-01 00:00:00
abstract：:The bioavailability of dipyridamole, a poorly soluble weak base, was evaluated in 11 healthy, older subjects (> or = 65 years), 6 with a low fasting gastric pH (control) and 5 with a fasting gastric pH > 5 (achlorhydric), in a randomized, crossover design. Subjects received 50 mg dipyridamole as a single oral dose bot...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1018918316253
更新日期：1994-01-01 00:00:00
abstract：:A fluorescence measurement system and methods of data analysis were developed to measure rapid kinetics of transdermal transport in vitro. Three variations on the technique were demonstrated, where the receptor compartment concentration was determined by: 1) fluorescence measurements of aliquots removed at discrete ti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016254013374
更新日期：1995-04-01 00:00:00
abstract：:The fluxes of nitroglycerine (NG) through human abdominal epidermis from different individuals were measured in vitro at 32°C. The mean NG flux for the entire group was 16.9 µg/cm(2) × hr, with a standard deviation of 47.7%. There are no significant differences in the means and the variances of NG fluxes between males...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/A:1016381017357
更新日期：1986-02-01 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：:Turbidimetric or light scattering assays can be used to determine the extent of aggregation in protein formulations. Using low molecular weight urokinase (LMW-UK) as a model protein, the effect of polymeric additives on heat-induced aggregation was evaluated. Previous work has shown that under 60 degrees C heat treatm...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018935420680
更新日期：1994-07-01 00:00:00
abstract：PURPOSE:To devise experimental and computational models to predict aqueous drug solubility. METHODS:A simple and reliable modification of the shake flask method to a small-scale format was devised, and the intrinsic solubilities of 17 structurally diverse drugs were determined. The experimental solubility data were us...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1014224900524
更新日期：2002-02-01 00:00:00
abstract：PURPOSE:The clinical utility of anthracyclines like idarubicin (IDA) is limited by the occurrence of multidrug resistance and cardiotoxicity. Previous studies have demonstrated that the multidrug transporter P-glycoprotein (P-gp) is present in the heart and have suggested that it exerts a protective function. We sought...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1013022212738
更新日期：2001-11-01 00:00:00
abstract：PURPOSE:To determine of the pharmacokinetic profile of methotrexate (MTX) in blood and extracellular fluid (ECF) of VX2 tumor and muscle in rabbits. METHODS:Microdialysis probes were inserted into VX2 tumor and in muscle tissue. Following intravenous administration of MTX (30 mg/kg), serial collection of arterial bloo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011973409022
更新日期：1998-01-01 00:00:00
abstract：PURPOSE:The purpose of this study was to investigate the effects of formulation factors including varying wax concentration, drug loading and drug particle size, on drug release characteristics from both pure oil and gel formulations prepared with a combination of derivatized vegetable oil (Labrafil 1944 CS) and glycer...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016209020160
更新日期：1995-06-01 00:00:00
abstract：:Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of n...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016247206531
更新日期：1995-05-01 00:00:00
abstract：:Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects ~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influenc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0951-x
更新日期：2013-03-01 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:Nanocrystalline drug-polymer dispersions are of significant interest in pharmaceutical delivery. The purpose of this work is to demonstrate the applicability of methods based on two-dimensional (2D) and multinuclear solid-state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen with pol...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0713-9
更新日期：2012-07-01 00:00:00
abstract：PURPOSE:The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs. METHODS:Preparation of the bicarbonate-containing dissolution medium was monitored by use...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1026147620304
更新日期：2003-10-01 00:00:00
abstract：PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000029294.70707.74
更新日期：2004-06-01 00:00:00
abstract：PURPOSE:Since the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2570-2
更新日期：2019-02-22 00:00:00
abstract：PURPOSE:To elucidate the apical and basolateral components of the total unstirred water layer in regular permeability experiment. METHODS:A novel stirring apparatus was constructed to remove the basolateral unstirred water layer. Caco-2 cells were used as the permeability barrier both in Transwell-type and side-by-sid...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9573-8
更新日期：2008-07-01 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: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:The aim of this study was to test the ability of paclitaxel-loaded poly(butylcyanoacrylate) (PBCA) nanoparticles to overcome multidrug resistance (MDR) in human ovarian resistant cells (A2780/T) and investigate its possible mechanism. METHODS:We prepared paclitaxel-loaded PBCA nanoparticles by interfacial poly...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-010-0346-9
更新日期：2011-04-01 00:00:00
abstract：PURPOSE:Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1636-z
更新日期：2015-07-01 00:00:00
abstract：:An empirical mass-transfer model for enteric-coating dissolution that uses in vivo dissolution data to characterize the pH-dependent solubility properties of the polymer film and a mass-transfer coefficient determined from in vivo dissolution or disintegration studies is developed. Once the in vivo mass-transfer coeff...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018986827350
更新日期：1993-02-01 00:00:00
abstract：:Human monocytes/macrophages (MO/MAC) were isolated from peripheral blood and cultivated on hydrophobic Teflon membranes. This culture system is suitable for HIV infection of MO/MAC in vitro. After transfer into 24-well plates the mature macrophages (infected or uninfected) were used for measurements of phagocytosis. T...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015852732512
更新日期：1992-04-01 00:00:00
abstract：PURPOSE:The purpose of this study was to use a replicate designed trial to assess the overall, intra- and inter-subject variabilities in pharmacokinetic parameters of CGP 33101 after oral administration of tablets relative to that of powder suspended in water, and to determine the relative proportion of the intra-subje...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1016275402723
更新日期：1995-12-01 00:00:00
abstract：PURPOSE:To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to produce fine powders of recombinant human deoxyribonuclease (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based solutions. METHODS:The ASES technique using high pressure carbon dioxide modified with e...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000008053.69903.c1
更新日期：2003-12-01 00:00:00
abstract：PURPOSE:To compare the effectiveness of trastuzumab-modified gold nanoparticles (AuNP) labeled with 177Lu (trastuzumab-AuNP-177Lu) targeted to HER2 with non-targeted AuNP-177Lu for killing HER2-overexpressing breast cancer (BC) cells in vitro and inhibiting tumor growth in vivo following intratumoral (i.t.) injection. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-2082-2
更新日期：2017-03-01 00:00:00
abstract：:The pharmacokinetics of trilostane and one of its metabolites ketotrilostane are described and characterized in the rat following the separate intravenous administration of trilostane and ketotrilostane. It was noted during these studies that the parent compound and its metabolite undergo metabolic interconversion-tri...
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：:The topical antifungal Sch-39304 is a racemic compound comprised of two enantiomers, Sch-42427 and Sch-42426, only one of which (Sch-42427) is pharmacologically active. The pure enantiomers have a lower melting point and, therefore, a higher solubility than the racemic compound. Because of these differences in physico...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018945618264
更新日期：1993-01-01 00:00:00
