Preclinical pharmacokinetic evaluation of resveratrol trimethyl ether in sprague-dawley rats: the impacts of aqueous solubility, dose escalation, food and repeated dosing on oral bioavailability.


:Resveratrol trimethyl ether (trans-3,5,4'-trimethoxystilbene, RTE) is a naturally occurring and pharmacologically active resveratrol derivative. To evaluate its suitability as a drug candidate, a pharmacokinetic study was carried out in Sprague-Dawley rats with the emphasis to identify the impact of aqueous solubility, dose escalation, food, and repeated dosing on its oral bioavailability. Upon single intravenous administration (5 mg/kg), RTE displayed moderate clearance (35.5 ± 5.3 mL/min/kg) and a fairly long terminal elimination half-life (511 ± 136 min); dose escalation (5-20 mg/kg) did not cause nonlinear pharmacokinetics. When given orally in suspension (60 mg/kg), RTE was poorly absorbed with negligible bioavailability (< 1.5%), fasting further decreased its bioavailability (<1%). However, when administered in a solution formulated with randomly methylated-β-cyclodextrin (15 mg/kg), RTE was rapidly absorbed with good bioavailability (46.5 ± 4.8%). Dose escalation resulted in increased bioavailability (64.6 ± 8.0%) at the dose of 60 mg/kg. Repeated RTE dosing (7 daily oral doses) did not alter the clearance, terminal elimination half-life and bioavailability. In summary, the aqueous solubility of RTE was a barrier to oral absorption; repeated RTE administrations did not alter its pharmacokinetic profiles; as RTE possessed appropriate pharmacokinetic profiles, further investigation on RTE as a drug candidate is warranted.


J Pharm Sci


Lin HS,Ho PC




Has Abstract


2011-10-01 00:00:00














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    abstract::Profiles of the steady-state concentrations of haloperidol (HL) and its major metabolite, reduced haloperidol (RHL), in plasma versus time were determined in 10 Japanese patients whose schizophrenic symptoms were clinically controlled by fixed, oral maintenance doses (4-30 mg/day, three times a day) for greater than 4...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Uematsu T,Matsuno H,Sato H,Hirayama H,Hasegawa K,Nakashima M

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  • Determination of enzyme or binding constants using generalized linear models, with particular reference to Michaelis-Menten models.

    abstract::The estimation of Michaelis-Menten pharmacokinetic parameters in patients with epilepsy receiving phenytoin continues to be a vexing problem. The various approximate methods suggested in the literature have serious shortcomings, primarily due to the role of the error term in the statistical model. In this report we pr...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: van Belle G,Leurgans S,Friel P,Guo SW,Yerby M

    更新日期:1989-05-01 00:00:00

  • Kinetics of drug-drug interactions in sheep: tolbutamide and sulfadimethoxine.

    abstract::The interaction between sulfadimethoxine and tolbutamide in sheep involving displacement from protein binding sites was investigated quantitatively. A 52% increase in the unbound plasma concentration of tolbutamide was observed in vitro at 37 degrees after the addition of sulfadimethoxine (100 microgram/ml) to sheep p...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Thiessen JJ,Rowland M

    更新日期:1977-08-01 00:00:00

  • Decomposition of alpha-hydroxyaryl ketones and characterization of some unusual products.

    abstract::Alpha-Hydroxyaryl ketones such as 2-hydroxypropiophenone and 1-(2,4-difluorophenyl)-2-hydroxy-1-propanone, the key intermediates in the preparation of antifungal agents, decompose into oxidized, rearranged, and condensed products. These products were isolated and characterized. The possible mechanisms for the formatio...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Gala D,Puar MS,Das PR,Kugelman M,DiBenedetto DJ

    更新日期:1992-12-01 00:00:00

  • Noninvasive identification of materials inside USP vials with Raman spectroscopy and a Raman spectral library.

    abstract::A commercial dispersive Raman spectrometer operating at 785 nm with a CCD detector was used to acquire spectra of USP reference materials inside amber USP vials. The laser and collection beams were directed through the bottom of the vials, resulting in a 60% loss of signal. The Raman shift was calibrated with a 4-acet...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: McCreery RL,Horn AJ,Spencer J,Jefferson E

    更新日期:1998-01-01 00:00:00

  • Compressibility of anhydrous tricalcium phosphate.

    abstract::It is shown that tricalcium phosphate follows a simple Heckel relationship in pressures of usual tablet compression, only if a density of 1.92 g/mL is used. This coincides with the density obtained by wet pycnometry, whereas the crystallographical density is 3.1 g/mL. The interpretation is that some of the pore space ...

    journal_title:Journal of pharmaceutical sciences

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    authors: Hou XP,Carstensen JT

    更新日期:1985-04-01 00:00:00

  • Carrier-mediated transport systems for glucose in mucosal cells of the human oral cavity.

    abstract::The in vitro uptake study was performed using the isolated cells of human oral mucosa, buccal and the dorsum of the tongue, to investigate the mechanisms of glucose uptake. The uptake of D-glucose was much larger in cells of the dorsum of the tongue than in buccal cells and was inhibited more extensively by 2-deoxy-D-...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 临床试验,杂志文章


    authors: Oyama Y,Yamano H,Ohkuma A,Ogawara K,Higaki K,Kimura T

    更新日期:1999-08-01 00:00:00

  • An investigation into the melting behavior of binary mixes and solid dispersions of paracetamol and PEG 4000.

    abstract::The melting behavior of paracetamol and polyethylene glycol (PEG) 4000, both individually and as binary systems, has been studied using differential scanning calorimetry. The appearance of the PEG peaks was shown to be highly dependent on scanning rate, with evidence for the existence of once-folded and extended chain...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Lloyd GR,Craig DQ,Smith A

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    abstract::An assay is described for the determination of the H2-receptor antagonist, cimetidine, in human plasma and urine. Alkalinized plasma or urine was extracted with methylene chloride, the organic phase was evaporated, and the reconstituted residue was analysed by high-pressure liquid chromatography (HPLC) using a reverse...

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    pub_type: 杂志文章


    authors: Mihaly GW,Cockbain S,Jones DB,Hanson RG,Smallwood RA

    更新日期:1982-05-01 00:00:00

  • Low-Molecular-Weight Heparin-Coated and Montelukast-Filled Inhalable Particles: A Dual-Drug Delivery System for Combination Therapy in Asthma.

    abstract::Montelukast, a cysteinyl leukotriene type 1 receptor antagonist, exhibits secondary anti-inflammatory properties when used at higher concentrations. Low-molecular-weight heparin (LMWH) evokes pronounced anti-inflammatory effects by interrupting leukocyte adhesion and migration. We hypothesized that inhalable particles...

    journal_title:Journal of pharmaceutical sciences

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    authors: Patel B,Rashid J,Gupta N,Ahsan F

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  • Stereoselective pharmacokinetics and inversion of suprofen enantiomers in humans.

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Shinohara Y,Magara H,Baba S

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  • Analysis and prediction of partition coefficients of meta- and para-disubstituted benzenes in terms of substituent effects.

    abstract::The hydrophobic substituent parameter for a system of meta- and para-disubstituted benzenes, XC6H4Y, defined as pi X/PhY = log PXC6H4Y - log PC6H5Y, where P is the octanol-water partition coefficient and X and Y are variable and fixed substituents, respectively, varies from one system to another, according to the vari...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Fujita T

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  • 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

  • Moisture sorption kinetics for water-soluble substances. I: Theoretical considerations of heat transport control.

    abstract::A model based on heat transport control was developed to describe the uptake of water on a deliquescent solid in an atmosphere of pure water vapor. The model assumes the presence of a saturated liquid film on the surface of the solid. The decrease in the vapor pressure of water over the surface, brought about by the c...

    journal_title:Journal of pharmaceutical sciences

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    authors: Van Campen L,Amidon GL,Zografi G

    更新日期:1983-12-01 00:00:00

  • Enhanced doxorubicin delivery to the brain administered through glutathione PEGylated liposomal doxorubicin (2B3-101) as compared with generic Caelyx,(®)/Doxil(®)--a cerebral open flow microperfusion pilot study.

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  • Stability-indicating assay for phenylbutazone: high-performance liquid chromatographic determination of hydrazobenzene and azobenzene in degraded aqueous phenylbutazone solutions.

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    authors: Fabre H,Hussam-Eddine N,Mandrou B

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  • Modeling of the Biological Activity of Monoclonal Antibodies Based on the Glycosylation Profile.

    abstract::The influence of the glycosylation profile of IgG on biological activity is known, but it is not clear which glycoforms have the highest impact on the main mechanism of action. The aim of this study was to design a mathematical model for predicting the antibody-dependent cellular cytotoxicity (ADCC) activity and the F...

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  • Preparation of pH-sensitive beads for NSAID using three-component gel systems.

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  • Crystal Structures and Phase Relationships of 2 Polymorphs of 1,4-Diazabicyclo[3.2.2]nonane-4-Carboxylic Acid 4-Bromophenyl Ester Fumarate, A Selective α-7 Nicotinic Receptor Partial Agonist.

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    journal_title:Journal of pharmaceutical sciences

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    authors: Hinderling PH,Roos A

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Wu Z,Razzak M,Tucker IG,Medlicott NJ

    更新日期:2005-05-01 00:00:00

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Kadir R,Stempler D,Liron Z,Cohen S

    更新日期:1987-10-01 00:00:00

  • Synthesis and evaluation of Ketorolac ester prodrugs for transdermal delivery.

    abstract::Alkyl esters of ketorolac were synthesized as potential prodrugs for transdermal delivery and evaluated to determine the relationship between their skin permeation characteristics and their physicochemical properties. Solubility of the prodrugs in various vehicles was determined at room temperature while lipophilicity...

    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Doh HJ,Cho WJ,Yong CS,Choi HG,Kim JS,Lee CH,Kim DD

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: de Siqueira JM,Carvalho S,Paniago EB,Tosi L,Beraldo H

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    journal_title:Journal of pharmaceutical sciences

    pub_type: 杂志文章


    authors: Planchon P,Pouillart P,Ronco G,Villa P,Pieri F

    更新日期:1993-10-01 00:00:00