Abstract：
:The expression of carboxylesterase (CES) and the transdermal movement of an ester prodrug were studied in rat skin. Ethyl-fexofenadine (ethyl-FXD) was used as a model lipophilic prodrug that is slowly hydrolyzed to its parent drug, FXD (MW 502). Among the CES1 and CES2 isozymes, Hydrolase A is predominant in rat skin and this enzyme was involved in 65% of the cutaneous hydrolysis of ethyl-FXD. The similarity of the permeation behavior of ethyl-FXD in full thickness and stripped skin indicated that the stratum corneum was not a barrier to penetration. However, only FXD was observed in receptor fluid, not ethyl-FXD, presumably because of the high degree of binding of ethyl-FXD in viable skin. The rate of hydrolysis of ethyl-FXD was much faster than steady-state flux, such that the influx rate was the rate-limiting process for transdermal permeation. Although Hydrolase A levels gradually increased in skin taken from rats aged from 8 to 90 weeks, variations in the expression levels of the esterase hardly affected the conversion of prodrug. The present data suggest that the slow hydrolysis of the prodrug of an active ingredient in viable skin followed by slow diffusion of active drug may provide a useful approach to topical application.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Imai T,Ariyoshi S,Ohura K,Sawada T,Nakada Ydoi
10.1002/jps.24648subject
Has Abstractpub_date
2016-02-01 00:00:00pages
714-721issue
2eissn
0022-3549issn
1520-6017pii
S0022-3549(15)00092-1journal_volume
105pub_type
杂志文章abstract：:The major route of degradation of tetrazepam (1) is oxidation to 7-chloro-5-(3-keto-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2-one (3) via the stable 7-chloro-5-(3-hydroperoxy-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H -1, 4 benzodiazepin-2-one (2). Minor degradation products are 7-chloro-5-(1,2-epoxy...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810216
更新日期：1992-02-01 00:00:00
abstract：:The aim of this study was to characterize the metabolic pathways of 2-methoxyestradiol (2ME2), an investigational anticancer drug. In vitro metabolism studies were performed by incubation of 2ME2 with human liver microsomes under various conditions and metabolite identification was performed using liquid chromatograph...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章
doi：10.1002/jps.20837
更新日期：2007-07-01 00:00:00
abstract：:Neural networks (NN) are computational systems implemented in software or hardware that attempt to simulate the neurological processing abilities of biological systems. A synopsis is presented of the operational characteristics, structures, and applications of NN. The NN technology has primarily been aimed at recognit...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820910
更新日期：1993-09-01 00:00:00
abstract：:A method for preparing polyanhydride granules of an injectable size was developed. The resulting granules permitted a nearly constant release of low-molecular-weight, water-soluble drugs without an initial burst. The polyanhydrides used were poly(fatty acid dimer), poly(sebacic acid), and their copolymers. The dyes ac...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830104
更新日期：1994-01-01 00:00:00
abstract：:6-Chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid hydrochloride lowered serum cholesterol, triglyceride, phospholipid, and free fatty acid levels in normal rats. The compound appeared to have a low toxicity and to be well tolerated in mice, adult and neonatal rats, and rabbits. At ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660311
更新日期：1977-03-01 00:00:00
abstract：:The effect of micellar sodium lauryl sulfate on the rate of cupric-ion-promoted hydrolysis of some dicarboxylic acid hemiesters was investigated at pH 5, ionic strength 0.1 M, and 40, 45, and 50 degrees. The rate of cupric-ion-promoted hydrolysis of sodium n-decyloxalate in the micellar phase is about 50 times as fast...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600651206
更新日期：1976-12-01 00:00:00
abstract：:To evaluate the potential of cell-penetrating peptide-based delivery of apoptosis-inducer gene in cancer therapy, a modified HIV-1 TAT peptide (dimerized TAT peptide, dTAT) was studied. The dTAT and plasmid DNA (pDNA) complexes (dTAT-pDNA) were condensed using calcium chloride (dTAT-pDNA-Ca2+). This simple nonviral fo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2016.08.023
更新日期：2017-01-01 00:00:00
abstract：:A rotating-basket apparatus for dissolution testing of veterinary bolus tablets was designed and constructed. Sulfamethazine boluses containing different disintegrating agents were evaluated in vitro and by blood level data following administration to cattle. The dissolution t50 and various pharmacokinetic parameters ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600651231
更新日期：1976-12-01 00:00:00
abstract：:Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbers...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661113
更新日期：1977-11-01 00:00:00
abstract：:Release of drug from a single-layer film containing dispersed drug follows a diffusion-controlled matrix model, where the quantity released per unit area is proportional to the square root of time. The kinetics may be made linear with time (zero order) by laminating a second film without drug to the releasing side of ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640806
更新日期：1975-08-01 00:00:00
abstract：:It is shown that a suitable dosage interval, tau, can be estimated by a factor times the sum of the mean residence time (MRT) of the central compartment (MRTC) and the MRT of the absorption site (MRTA). This value of tau will provide a ratio, maximum steady-state plasma concentration: minimum steady-state plasma conce...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760111
更新日期：1987-01-01 00:00:00
abstract：:The association efficiency of oxytetracycline (OTC) to pharmaceutical available, ionic oil-in-water nanoemulsions is studied. Theoretical mathematical developments allowed us to differentiate by diafiltration (DF) between thermodynamically and kinetically controlled binding of the drug to the nanoemulsions, and relate...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24255
更新日期：2015-03-01 00:00:00
abstract：:The effect of variable protein binding (taken as independent parameter) on pharmacological activity of drugs is considered in terms of the exposure or the steady state concentration of unbound drug at targeted tissue. Based on the application of the parallel tube or dispersion models it is shown that for the most comm...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21958
更新日期：2010-04-01 00:00:00
abstract：:A study was undertaken to develop a method that could be used an an indication of the absorption of steroids. It was demonstrated that 17-hydroxycorticosteroids in urine could be quantitatively determined via absorptivity values obtained through the use of standard hydrocortisone-alcohol solutions or standard solution...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640643
更新日期：1975-06-01 00:00:00
abstract：:An ethanol extract of the root of a Mexican variant of Cannabis sativa L.(marijuana) afforded, after partitioning and chromatography, the new spermidine alkaloid cannabisativine. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650736
更新日期：1976-07-01 00:00:00
abstract：:Aqueous solubilities for some guanine derivatives were estimated by semiempirical equations developed by Yalkowsky and Valvani1 using the data for partition coefficient and melting temperature. It was shown that in the case of guanine derivatives examined in this study, the solubility values could not be estimated ade...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980180z
更新日期：1999-01-01 00:00:00
abstract：:The mechanism of organic solvent evaporation during microencapsulation and its role during microsphere hardening has been investigated. Evaporation and encapsulation studies were carried out in a jacketed beaker, filled with aqueous hardening solution, which was maintained at constant temperature and constant stirring...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:The oral absorption of drugs has been represented by various concepts such as the absorption potential, the maximum absorbable dose, the biopharmaceutics classification system, and in vitro-in vivo correlation. The aim of this article is to provide an overview of the theoretical relationships between these concepts. I...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.24391
更新日期：2015-09-01 00:00:00
abstract：:The phase diagram for the binary system nafcillin sodium-water, was determined using differential scanning calorimetry (DSC) and polarized light microscopy. In the temperature range of -20-30 degrees, three crystalline forms and an amphiphilic liquid crystalline phase were detected. The stable crystalline form of nafc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710125
更新日期：1982-01-01 00:00:00
abstract：:The granule strength (crushing load) of lactose granulated with 1-9% povidone was measured initially and at intervals during a 1-year period. The granule strengths of dibasic calcium phosphate dihydrate granulated with various concentrations of starch and povidone were measured. The axial and radial tensile strengths ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600720513
更新日期：1983-05-01 00:00:00
abstract：:A method that accurately indicates the end-point of precipitation reactions by the measurement of the relative intensity of the scattered light in the titrate is presented. A new nephelometric titrator with an internal nephelometric sensor has been devised. The work of the titrator including the sensor and change in t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10548
更新日期：2004-02-01 00:00:00
abstract：:Ascorbic acid (100 mg/ml) and sodium bisulfite (0.5 and 20 mg/ml) prevented more than 10% oxidation of apomorphine hydrochloride in water maintained at room temperature over 1-3 days. Refrigeration at 5 degrees prevented oxidation of apomorphine hydrochloride in aqueous solutions for 1 week. Neither ascorbic acid nor ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690830
更新日期：1980-08-01 00:00:00
abstract：:A method for the measurement of a potential diuretic-antihypertensive agent, (+/-)-[[6,7-dichloro-2-(4-fluorophenyl)-2-methyl-1-oxo-5-indanyl] oxy]acetic acid, in biological fluids is described. The procedure involves the addition of a related internal standard to the specimens followed by extraction of the acids into...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730234
更新日期：1984-02-01 00:00:00
abstract：:Tissue damage caused by subcutaneous and intramuscular administration of three phenytoin prodrugs to rats was assessed. Since two of the prodrugs caused significant irritation, only 3-(hydroxymethyl)-5,5-diphenylhydantoin disodium phosphate ester might be useful as a nonirritant phenytoin prodrug suitable for parenter...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730815
更新日期：1984-08-01 00:00:00
abstract：:Simple and sensitive enzyme immunoassays (EIAs), discriminating a new angiotensin-converting enzyme (ACE) inhibitor, cilazapril [9(s) - [1(s)-(ethoxycarbonyl)-3-phenylpropylamino]-octahydro-10-oxo-6H- pyridazo[1,2-a] [1,2]diazepine-1(s)carboxylic acid] and its active metabolite [9(s)-[1(s)-carboxy-3-phenylpropylamino]...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600760308
更新日期：1987-03-01 00:00:00
abstract：:Cephalosporins are among the most frequently used broad-spectrum antimicrobial agents. Ceftazidime is a semisynthetic β-lactam antibiotic for parenteral administration widely used in the clinical practice, which has been categorized as a third-generation cephalosporin antibiotic. This drug crystallizes as a pentahydra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2019.11.018
更新日期：2020-03-01 00:00:00
abstract：:Current drug level predictions in nonlinear pharmacokinetics are based on specific pharmacokinetic models in contrast to the model-independent (structureless), dose-linearity, and superposition principles used in linear pharmacokinetics. Such model-dependent methods may not provide reliable predictions due to their in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730614
更新日期：1984-06-01 00:00:00
abstract：:Taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere) are promising agents for use against ovarian cancer and other malignancies. Recently, SB-T-1011, a semisynthetic taxane, has been prepared from 14-hydroxy-10-deacetylbaccatin III. SB-T-1011 shows similar or greater in vitro cytostatic activity than paclitaxel...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600841204
更新日期：1995-12-01 00:00:00
abstract：:The influence of different types of absorbents on moisture transmission through free (cast films) and applied (coated tablets) polymer films was investigated. In free film studies, lubricated granulations were considered to be the absorbent. The compressed tablet was considered to be the absorbent in applied film stud...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650411
更新日期：1976-04-01 00:00:00
abstract：:Results of studies carried out in rats for model compounds, D-(-) mandelic acid, benzoylformic acid, and some of their para-alkylated homologs, showed that their biological half-lives determined from the elimination phase of urinary excretion data were longer than those determined from the elimination phase of blood l...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650920
更新日期：1976-09-01 00:00:00
