Improved anticonvulsant activity of phenytoin by a redox brain delivery system. III: Brain uptake and pharmacological effects.


:Phenytoin (DPH) was delivered to the brain by a dihydropyridine in equilibrium pyridinium salt redox system, which was evaluated for anticonvulsant activity. Following iv injection of the lipophilic delivery system of DPH (2) to rats, concentrations of DPH were lower but sustained and, after 30 min, essentially the same as the levels after equimolar administration of DPH. While 2 delivered the same levels of DPH to the brain as DPH did, it was twice as potent as DPH in rats (ED50 was 7.5 mumol/kg for 2 and 14.2 mumol/kg for DPH) and mice (2: 10.5; DPH: 23.9) against maximal electroshock seizures (MES), and seven times more potent in mice (2: 10.0, DPH: 70.6) against maximal pentylenetetrazole seizures (MPS). Moreover, 2 was active against pentylenetetrazole threshold seizures (PTS) in mice and rats (ED50 = 44.1 and 40.5 mumol/kg, respectively), while DPH was ineffective (up to a dose of 79.2 mumol/kg). After evaluation of acute neurological toxicity in rats, 2 was found to possess 1.5 times higher a protective index (for MES) than DPH. It appeared also that while DPH was 2.9 times less sensitive to MPS than to MES, 2 was equally potent to both types of convulsions. Thus, the data indicate that 2 delivered DPH more efficiently to the brain. The better anticonvulsant activity (quantitatively as well as qualitatively) of 2 can be explained on the basis of an improved distribution in the brain due to its higher lipophilicity, and by favorable regional differences in the rates of conversion of 2 to DPH at the convulsing foci.


J Pharm Sci


Shek E,Murakami T,Nath C,Pop E,Bodor NS




Has Abstract


1989-10-01 00:00:00














  • Influence of asymmetric donor-receiver ion concentration upon transscleral iontophoretic transport.

    abstract::Recent in vitro and in vivo studies have suggested transscleral iontophoresis as a means for non-invasive drug delivery to the eye. However, there remains a lack of information of the iontophoretic transport behavior of the sclera. The objective of the present study was to investigate the effects of permeant concentra...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Li SK,Zhang Y,Zhu H,Higuchi WI,White HS

    更新日期:2005-04-01 00:00:00

  • Improving Dissolution Properties by Polymers and Surfactants: A Case Study of Celastrol.

    abstract::Two polymorphs of celastrol were discovered and fully characterized by X-ray powder diffraction, thermogravimetry analysis, and differential scanning calorimetry. The single-crystal structures of form I and the isostructural solvate of form II were disclosed by single-crystal X-ray diffraction. The apparent solubility...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Zha J,Zhang Q,Li M,Wang JR,Mei X

    更新日期:2018-11-01 00:00:00

  • Application of gas pycnometry for the density measurement of freeze-dried products.

    abstract::Gas pycnometry is applied to determine the density of solid materials. The analysis of lyophilisates is particularly challenging because of their porous structure. In this study, the density of raw materials and freeze-dried products was determined using different pycnometric methodologies and gases [helium (He), nitr...

    journal_title:Journal of pharmaceutical sciences

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    authors: Stange U,Scherf-Clavel M,Gieseler H

    更新日期:2013-11-01 00:00:00

  • Antibacterial activity of 6,8-disubstituted-quinolone-3-carboxylic acids.

    abstract::Twelve 6,8-disubstituted-1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid derivatives were prepared and evaluated for their antibacterial activity. Among these, only the 6,8-difluoroquinolinone-3-carboxylic acid showed moderate activity. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Krishnan R,Lang SA Jr

    更新日期:1986-12-01 00:00:00

  • Physicochemical characterization of nedocromil bivalent metal salt hydrates. 3. Nedocromil calcium.

    abstract::A crystalline pentahydrate and a crystalline 8/3 hydrate of nedocromil calcium (NC) were prepared. The relationships between these solid phases and the nature of the water interactions in their structures were studied through characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)...

    journal_title:Journal of pharmaceutical sciences

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    authors: Zhu H,Halfen JA,Young VG Jr,Padden BE,Munson EJ,Menon V,Grant DJ

    更新日期:1997-12-01 00:00:00

  • Nonadditive Effects of Repetitive Administration of Lipoplexes in Immunocompetent Mice.

    abstract::Repetitive administration is routinely used to maintain therapeutic drug levels, but previous studies have documented an accelerated blood clearance of some lipid-based delivery systems under these conditions. To assess the effect of repetitive administration, non-PEGylated lipoplexes (+/-0.5) were administered 4 time...

    journal_title:Journal of pharmaceutical sciences

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    authors: Betker JL,Anchordoquy TJ

    更新日期:2017-03-01 00:00:00

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    abstract::Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within...

    journal_title:Journal of pharmaceutical sciences

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    authors: Wu IY,Nikolaisen TE,Škalko-Basnet N,di Cagno MP

    更新日期:2019-08-01 00:00:00

  • In situ monitoring of polymorph transformation of clopidogrel hydrogen sulfate using measurement of ultrasonic velocity.

    abstract::Transformation of polymorph I of clopidogrel hydrogen sulfate (CHS) to polymorph II of CHS during the crystallization was monitored by using in situ measurement of ultrasonic velocity. Drowning-out crystallization using methanol as a solvent and isopropyl alcohol as nonsolvent was carried out. The polymorphs were iden...

    journal_title:Journal of pharmaceutical sciences

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    authors: Kim HJ,Kim KJ

    更新日期:2008-10-01 00:00:00

  • Theoretical description of transdermal transport of hydrophilic permeants: application to low-frequency sonophoresis.

    abstract::Application of ultrasound enhances transdermal transport of drugs (sonophoresis). The enhancement may result from enhanced diffusion due to ultrasound-induced skin alteration and/or from forced convection. To understand the relative roles played by these two mechanisms in low-frequency sonophoresis (LFS, 20 kHz), a th...

    journal_title:Journal of pharmaceutical sciences

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    authors: Tang H,Mitragotri S,Blankschtein D,Langer R

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  • Quantitative Analysis of the Transporter-Mediated Drug-Drug Interaction Between Atorvastatin and Rifampicin Using a Stable Isotope-IV Method.

    abstract::This study aims to investigate the drug-drug interactions (DDIs) between orally administered atorvastatin (ATV) and rifampicin (RIF) in rats. The isotope-IV method was used for the analysis of the increased systemic exposure (AUCpo) of ATV, in which a small amount of deuterium-labeled ATV (ATV-d5) was intravenously in...

    journal_title:Journal of pharmaceutical sciences

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    更新日期:2017-09-01 00:00:00

  • Overall monotropic behavior of a metastable phase of biclotymol, 2,2'-methylenebis(4-chloro-3-methyl-isopropylphenol), inferred from experimental and topological construction of the related P-T state diagram.

    abstract::The melt from the usual monoclinic phase (Phase I) of biclotymol (T(fusI) = 400.5 +/- 1.0 K, Delta(fus)H(I) = 36.6 +/- 0.9 kJ mol(-1)) recrystallizes into another phase, Phase II, that melts at T(fusII) = 373.8 +/- 0.2 K (Delta(fus)H(II) = 28.8 +/- 1.0 kJ mol(-1)). The transformation of Phase II into Phase I is found ...

    journal_title:Journal of pharmaceutical sciences

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    authors: Céolin R,Tamarit JL,Barrio M,López DO,Nicolaï B,Veglio N,Perrin MA,Espeau P

    更新日期:2008-09-01 00:00:00

  • Comprehensive high-performance liquid chromatographic methodology for the determination of thiothixene in bulk drug, finished product, and dissolution testing samples.

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Severin G

    更新日期:1987-03-01 00:00:00

  • High-throughput determination of the free fraction of drugs strongly bound to plasma proteins.

    abstract::Quantification of protein binding of new chemical entities is an important early screening step during drug discovery and is of fundamental interest for the estimation of safety margins during drug development. In this publication, we describe the development of a new high-throughput assay for the determination of the...

    journal_title:Journal of pharmaceutical sciences

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    authors: Schuhmacher J,Kohlsdorfer C,Bühner K,Brandenburger T,Kruk R

    更新日期:2004-04-01 00:00:00

  • Application of one-phase end-point change system in two-phase titration to amine drug analysis.

    abstract::A titration method was developed for the determination of diphenhydramine, quinine, neostigmine, sparteine, strychnine, homatropine, atropine, physostigmine, and procaine in aqueous solution. Tetraphenylborate was used as a titrant with tetrabromophenolphthalein ethyl ester as an indicator in the presence of organic s...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Tsubouchi M,Mitsushio H,Yamasaki N,Matsuoka K

    更新日期:1981-11-01 00:00:00

  • Effect of inorganic additives on solutions of nonionic surfactants V: Emulsion stability.

    abstract::Electrolytes often break emulsions to which they were added as active ingredients, adjuvants, or impurities. The stability of oil-in-water emulsions containing octoxynol 9 NF as the emulsifier and various added electrolytes was investigated by measuring droplet size, turbidity, and oil separation on storage at various...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Schott H,Royce AE

    更新日期:1983-12-01 00:00:00

  • Trace decomposition of selegiline. Use of worst-case kinetics for a stable drug.

    abstract::A solution of selegiline hydrochloride reference standard, which contained no detectable impurities at the time of its preparation, was found by HPLC to contain a trace of a compound at the locus of methamphetamine when analyzed after 1 year. Heating selegiline solutions at pH 7 and 105 degrees C produced methamphetam...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Chafetz L,Desai MP,Sukonik L

    更新日期:1994-09-01 00:00:00

  • Bioavailability of sulfadiazine in rabbits using tablets prepared by direct compression and fluidized-bed granulation.

    abstract::Experimental sulfadiazine tablets prepared by direct compression, using a commercially available direct compression tablet mass, were compared with experimental sulfadiazine tablets prepared by fluidized-bed granulation and commercially available sulfadiazine tablets USP. The values for friability and the time require...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Ritschel WA,Erni W

    更新日期:1977-10-01 00:00:00

  • Targeted Drug Delivery via Folate Receptors for the Treatment of Brain Cancer: Can the Promise Deliver?

    abstract::Brain cancers are among the most lethal tumors due to their rapid development and poor prognosis. Despite the existing potential of novel therapeutic strategies for the treatment of brain cancer, the major remaining challenge associated with clinical translation is the lack of effective and safe delivery strategies to...

    journal_title:Journal of pharmaceutical sciences

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    authors: Guo J,Schlich M,Cryan JF,O'Driscoll CM

    更新日期:2017-12-01 00:00:00

  • Synthesis and antibacterial evaluation of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles.

    abstract::The synthesis and antibacterial evaluation of a number of 2-(substituted phenylureido)-4-thiocyanatobenzothiazoles are described. The more active compounds against the test organisms in vitro generally were those substituted with halogens on the phenyl and benzothiazole rings. ...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Alaimo RJ,Pelosi SS,Freedman R

    更新日期:1978-02-01 00:00:00

  • Determination of bacmecillinam, an amdinocillin prodrug, in human and canine whole blood by reversed-phase liquid chromatography.

    abstract::Bacmecillinam is an amdinocillin prodrug designed to be easily hydrolyzed in biological materials, so special procedures were developed for the collection of blood specimens. Whole blood was collected in tubes containing bacampicillin as an adsorption inhibitor and kept at -70 degrees; the extracting solvent, hexane-m...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Westerlund D,Pettersson B,Carlqvist J

    更新日期:1982-10-01 00:00:00

  • Adsorption of cationized bovine serum albumin onto epithelial crypt fractions of the rat colon.

    abstract::The purpose of the study was to characterize mucosal attachment of a cationized model protein, bovine serum albumin (BSA), onto the various fractions of colonic crypts epithelium in the rat. BSA was labeled with fluorescein isothiocyanate (FITC) and its surface net electric charge was modified from negative to positiv...

    journal_title:Journal of pharmaceutical sciences

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    authors: Blau S,Levin N,Schwartz B,Rubinstein A

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  • Serum lipid-lowering properties of 6-chloro-9-[2-(6-methyl-3-pyridyl)ethyl]-1,2,3,4-tetrahydrocarbazole-2-carboxylic acid.

    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


    authors: Dalton C,Pool WR

    更新日期:1977-03-01 00:00:00

  • Solubility and mass and nuclear magnetic resonance spectroscopic studies on interaction of cyclosporin A with dimethyl-alpha- and -beta-cyclodextrins in aqueous solution.

    abstract::The interaction of cyclosporin A (CsA) with dimethyl-alpha- and -beta-cyclodextrins (DM-alpha-CyD and DM-beta-CyD) was investigated by the solubility method, electrospray ionization mass spectrometry (ESI-MS) and 1H-nuclear magnetic resonance spectroscopy (1H NMR). The extremely low solubility (1.9 x 10(-5) M at 25 de...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Miyake K,Hirayama F,Uekama K

    更新日期:1999-01-01 00:00:00

  • Kinetics of drug action in disease states. XXXVIII: Effect of body temperature on the convulsant activity of pentylenetetrazol in rats.

    abstract::The purpose of this investigation was to determine the effect of body temperature on the pharmacodynamics (convulsant activity) of pentylenetetrazol (PTZ). Rats received an iv infusion of PTZ until the onset of maximal seizures, at which time samples of cerebrospinal fluid (CSF), brain, and blood (for serum) were obta...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Walker JS,Levy G

    更新日期:1991-10-01 00:00:00

  • On-line clean-up system of plasma sample for simultaneous determination of morphine and its metabolites in cancer patients by high-performance liquid chromatography.

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Konishi M,Hashimoto H

    更新日期:1990-05-01 00:00:00

  • Self-setting hydroxyapatite cement: a novel skeletal drug-delivery system for antibiotics.

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Yu D,Wong J,Matsuda Y,Fox JL,Higuchi WI,Otsuka M

    更新日期:1992-06-01 00:00:00

  • Systematic Evaluation of Wajima Superposition (Steady-State Concentration to Mean Residence Time) in the Estimation of Human Intravenous Pharmacokinetic Profile.

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    pub_type: 杂志文章


    authors: Lombardo F,Berellini G,Labonte LR,Liang G,Kim S

    更新日期:2016-03-01 00:00:00

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Taylor T,Chasseaud LF

    更新日期:1977-11-01 00:00:00

  • Solubilization of ionized and un-ionized flavopiridol by ethanol and polysorbate 20.

    abstract::Because the ionized species is more polar than its un-ionized counterpart, it is often assumed that the ionized species of the drug does not make a meaningful contribution to solubilization by either cosolvents or surfactants. This report extends previous studies on solubilization of the ionic species by a combination...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Li P,Tabibi SE,Yalkowsky SH

    更新日期:1999-05-01 00:00:00

  • Adsorption of pepsin by aluminum hydroxide II: Pepsin inactivation.

    abstract::Pepsin adsorbed on gibbsite or boehmite, non-acid-reactive forms of aluminum hydroxide, had a significantly lower activity than pepsin in solution. IR and desorbed pepsin activity studies showed that the reduced activity of adsorbed pepsin was not due to denaturation of pepsin on adsorption. Steric occlusion of the ac...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Sepelyak RJ,Feldkamp JR,Regnier FE,White JL,Hem SL

    更新日期:1984-11-01 00:00:00