Abstract：
:A physical model approach to the topical delivery of a vidarabine ester prodrug was investigated. It involved modeling, theoretical simulations, experimental method development for factoring and quantifying parameters, and, finally, employment of the deduced parameters to determine the steady-state species fluxes and concentration profiles in the target tissue. The present report describes the physical modeling and theoretical simulation aspects. The physical model for the simultaneous transport and bioconversion of a topically delivered prodrug was formulated assuming homogeneous enzyme distributions and constant diffusivities in the membrane. The mathematical problem was solved, and the solution yielded concentration profiles and fluxes of all species in the biomembrane. These results provided the prevailing levels of the prodrug, the drug, and the metabolite at the target site and the transport rates of all species into the bloodstream. Computations of concentration profiles and fluxes were carried out for a reasonable range of the parameters. The relative activities of the esterase and the deaminase enzymes, as well as the stratum corneum permeabilities, were important in influencing the concentration profiles and fluxes of all species.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Yu CD,Fox JL,Ho NF,Higuchi WIdoi
10.1002/jps.2600681104subject
Has Abstractpub_date
1979-11-01 00:00:00pages
1341-6issue
11eissn
0022-3549issn
1520-6017pii
S0022-3549(15)42924-7journal_volume
68pub_type
杂志文章abstract：:Nonviral, plasmid-based therapeutics are a new class of pharmaceutical agents that offer the potential to cure many diseases that are currently considered untreatable. While nonviral vectors have shown promise in clinical trials, their physical instability in liquid formulations represents a major barrier to the devel...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/(SICI)1520-6017(200003)89:3<289::AID-JPS1>
更新日期：2000-03-01 00:00:00
abstract：:A recirculation technique was used to study the first-order kinetics of intestinal absorption of un-ionized sulfadiazine, sulfamerazine, and sulfamethazine in rats in situ at 32, 35, and 38 degrees C. The absorption rate constant (Kab) of each sulfonamide increased with increase in temperature and, at each temperature...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600821208
更新日期：1993-12-01 00:00:00
abstract：:Prostaglandin F2 alpha was administered intraamniotically to 132 mid-first trimester gravidas to determine the dose-24-hour abortifacient response relationship. Single doses between 15-50 mg and multiple doses between 15-25 mg were administered to 3 groups each, the latter regimen at 6-hour intervals. Trials were de...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600620809
更新日期：1973-08-01 00:00:00
abstract：:Hemoglobin microcapsules were prepared through cross-linking of hemoglobin itself with various acyldichlorides. Variations in the reticulation conditions were preformed in order to ameliorate the oxygen dissociation curve, the mean diameter, and the possibility for the microcapsules to be lyophilized. With terephthalo...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710710
更新日期：1982-07-01 00:00:00
abstract：:An exsorption technique which can assess the transport of a drug from blood to the intestinal lumen was used to study the effects of glucose and to determine the presence of segmental differences in drug transport across the rat small intestinal membrane following intravenous drug administration. The drugs used in the...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600740319
更新日期：1985-03-01 00:00:00
abstract：:Sustained-release formulations such as hydroxypropyl methylcellulose (HPMC)-based hydrophilic matrix tablets of poorly water-soluble drugs often result in incomplete release because of the poor solubility and dissolution rate of the drug in the hydrophilic matrix. Sulfobutylether-beta-cyclodextrins ((SBE)(7M)-beta-CDs...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1034
更新日期：2001-07-01 00:00:00
abstract：:A modification of wet agglomeration technique is developed and demonstrated by agglomerative crystallization process for a nonapeptide (ABT-510) to improve processing of needle like crystals. Our procedure involves exploiting partial miscibility of the crystallization solvent system for in situ generation of a wetting...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21063
更新日期：2008-03-01 00:00:00
abstract：:A series of substituted 3-(benzylideneamino) coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedmatous activity, respectively (phenylbutazone antiedematous activity, 58%...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810926
更新日期：1992-09-01 00:00:00
abstract：:A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a conveni...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640826
更新日期：1975-08-01 00:00:00
abstract：:A method is presented for encapsulating high molecular weight biological materials such as viral antigen, concanavalin A, and other proteins with cellulose acetate phthalate. The method is simple, inexpensive, and rapid; the process takes approximately 15 min. Capsules generated by this method are produced as microsph...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600730110
更新日期：1984-01-01 00:00:00
abstract：:Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of DNSA incre...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20203
更新日期：2004-12-01 00:00:00
abstract：:Solid samples of 1-hydroxymethyl- and 1,5-dihydroxymethylallopurinol, 1-hydroxymethylglutethimide, and 1-hydroxymethylphenobarbital were prepared, and equilibrium constants for their formation from formaldehyde and allopurinol, glutethimide, or phenobarbital were calculated. The N-hydroxymethyl derivatives had higher ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600700804
更新日期：1981-08-01 00:00:00
abstract：:The effects of milling and compression on the solid-state Maillard reaction between metoclopramide hydrochloride and lactose were investigated. Anhydrous metoclopramide hydrochloride was milled for various times, and then mixed with amorphous lactose. The mixtures were stored at 105 degrees C and 0% RH. The reactivity...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20448
更新日期：2005-11-01 00:00:00
abstract：:Spectrophotometric assay for cycloserine based on the interaction of the drug with 9-methoxyacridine as a chromogenic agent is described. The highly colored substituted acridine product was identified as 9-(d-4-imino-3-isoxazolidinone)acridine. Color development was affected by time and temperature of heating and by t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770519
更新日期：1988-05-01 00:00:00
abstract：:Flightless I (Flii) is an actin remodeling protein important for cytoskeletal regulation and cellular processes including migration, proliferation, and adhesion. Previous studies have clearly identified Flii as a novel therapeutical target for improved wound repair and have demonstrated Flii regulation using Flii neut...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.03.012
更新日期：2017-07-01 00:00:00
abstract：:The capacity factors of several penicillins and cephalosporins, as well as those of 7-aminocephalosporanic acid, 6-aminopenicillanic acid, and 7-aminodeacetoxycephalosporanic acid, were determined at pH 2.5-7.5 with different methanol concentrations in the mobile phase. The influence of ionic strength on activity fact...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600690506
更新日期：1980-05-01 00:00:00
abstract：:A specific, sensitive, rapid, and reproducible analytical GLC method for lidocaine in human plasma, including pharmacokinetic parameters, is described. Aminopyrine is the internal standard. The method was used to study pharmacokinetics in four healthy volunteers following the administration of a lidocaine bolus at a d...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600661007
更新日期：1977-10-01 00:00:00
abstract：:Male and female rats treated with a single 20-mg/kg ip dose of pregnenolone-16alpha-carbonitrile (PCN) produced parallel increases in hepatic cytochrome P-450 and aniline hydroxylase activity. However, the onset of increase in aniline hydroxylase activity and cytochrome P-450 content was slower in male than female ani...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650436
更新日期：1976-04-01 00:00:00
abstract：:A method is described for the analysis of amitriptyline, doxepin, imipramine, nortriptyline, desmethyldoxepin, desipramine, and protriptyline in human plasma utlizing GLC-chemical-ionization mass spectrometry with selected ion monitoring. The assay is highly specific and is quantitative to at least 1 ng/ml with a stan...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670106
更新日期：1978-01-01 00:00:00
abstract：:To gain further insight into the effect of molecular mobility on the crystallization rate of amorphous drugs, the mean relaxation times of amorphous nifedipine and phenobarbital were calculated based on the Adam-Gibbs-Vogel (AGV) equation, using the parameters D, T(0), and T(f), derived from the heating rate dependenc...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.1033
更新日期：2001-06-01 00:00:00
abstract：:The effect of chemical penetration enhancers (e.g., fatty acids) in combination with iontophoresis was examined on the in vitro permeability of luteinizing hormone releasing hormone (LHRH) through porcine skin. Porcine epidermis was pretreated with either ethanol (EtOH) or 10% fatty acid/EtOH. The permeability coeffic...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js970301f
更新日期：1998-04-01 00:00:00
abstract：:An aqueous solution of trimedoxime bromide, atropine, and benactyzine hydrochloride was formulated to have maximum stability as an antidote in organophosphorus poisoning. The stability of the mixture in glass and plastic cartridges was determined. Glass cartridges were more desirable than plastic; there was less vapor...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600710315
更新日期：1982-03-01 00:00:00
abstract：:A single method for the quantitative determinations of three active ingredients, phenylephrine hydrochloride, phenylpropanolamine hydrochloride, and brompheniramine maleate, and one inactive ingredient (sodium benzoate) in a commercial product for colds is reported. The method is based on paired ion high-pressure liqu...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670643
更新日期：1978-06-01 00:00:00
abstract：:Synthetic peptides corresponding to the variable tandem repeat domain of the cancer-associated antigen MUC1 mucin are candidates for cancer vaccines. In our investigation mice were immunized via subcutaneous injection with poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres containing a MUC1 mucin peptide. It was hy...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980070s
更新日期：1998-11-01 00:00:00
abstract：:Virtually all biological variables, including those affected by drugs, are subject to adaptive self regulation. In the description of the pharmacodynamics (PD) of drugs, it may be necessary to consider the endogenous control system (ECS) as an integral part of the PD. A PDECS model based on system analysis principles ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600820310
更新日期：1993-03-01 00:00:00
abstract：:Various complex mechanisms and their multifactorial pathways decisively provoke low-grade local and systemic inflammation in β-cells of pancreatic islets and peripheral tissues to induce β-cells' dysfunction and apoptosis, insulin resistance, and ultimately, overt type 2 diabetes mellitus (T2DM). Conventional antidiab...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1002/jps.23057
更新日期：2012-05-01 00:00:00
abstract：:The binding of acetazolamide to human erythrocytes was studied in vitro. Blood and plasma samples were analyzed by electron-capture GLC. At 37 degrees, drug equilibrated between plasma and erythrocytes in approximately 40 min. The effect of plasma concentration on the steady-state level of drug within the erythrocytes...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600660532
更新日期：1977-05-01 00:00:00
abstract：:Time and resource constraints necessitate increasingly early decision making to accelerate or stop preclinical drug discovery programs. Early discovery drug candidates may be potent inhibitors of new targets, but all too often exhibit poor pharmaceutical and pharmacokinetic properties that limit the in vivo exposure. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.22092
更新日期：2010-07-01 00:00:00
abstract：:The location and conformation of fosinopril sodium (FS) in a lamellar liquid crystal of water, sodium dodecyl sulfate, and decanol was studied by low-angle X-ray diffraction. The result showed the FS molecule to be located within the amphiphilic part of the liquid crystalline structure with the polar parts anchored at...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600830517
更新日期：1994-05-01 00:00:00
abstract：:The hepatic distribution, biliary excretion, and mass balance of liposomal amphotericin B (L-AmB) were investigated in recirculated isolated perfused rat liver. The results were compared with those from the conventional AmB formulation, amphotericin B deoxycholate (D-AmB). L-AmB was introduced as a bolus into the perf...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20239
更新日期：2005-01-01 00:00:00
