当前位置： SCI文献检索 > PHARMACEUTICAL RESEARCH期刊下所有文献 > A fractal approach to heterogeneous drug distribution: calcium pharmacokinetics.

A fractal approach to heterogeneous drug distribution: calcium pharmacokinetics.

Abstract：

PURPOSE:To point out the importance of heterogeneity in drug distribution processes and develop a noncompartmental approach for the description of the distribution of drug in the body. METHODS:A dichotomous branching network of vessels for the arterial tree connected to a similar venous network was used to describe the heterogeneity of blood flow in the successive generations of the networks. The relevant kinetics of drug distribution in the well perfused and the deep tissues was considered to take place under well stirred (homogeneous) and understirred (heterogeneous) conditions, respectively. RESULTS:A "homogeneous model" with classical kinetics (which is mathematically equivalent with the one-compartment model) was developed for these drugs which are confined to well perfused ("well stirred") spaces. A "heterogeneous model" was proposed for the drugs reaching understirred spaces using a decreasing with time rate coefficient (fractal kinetics) to model the diffusion of drug under heterogeneous conditions. The analysis of the model equations revealed that the homogeneous model can be considered as a special case of the heterogeneous model. Concentration-time plots of multiexponential type were generated using the heterogeneous model equation. The empirically used power functions of time for the analysis of calcium clearance curves, were found to be similar to the equation adhering to the heterogeneous model. Fittings comparable to multiexponential models were obtained when the heterogeneous model equation with only one adjustable parameter was applied to six sets of long period calcium data. CONCLUSIONS:The heterogeneous processes of drug distribution in the body can obey the principles of fractal kinetics. Calcium clearance curves were analysed with the heterogeneous model. The validity of multicompartmental models which are based on the concept of homogeneity to describe drug distribution should be reconsidered.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Macheras P

doi

10.1023/a:1016031129053

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

663-70

issue

5

eissn

0724-8741

issn

1573-904X

journal_volume

13

pub_type

杂志文章

相关文献

PHARMACEUTICAL RESEARCH文献大全
  • Physiologically based pharmacokinetic model for composite nanodevices: effect of charge and size on in vivo disposition.

    abstract：PURPOSE:To characterize temporal exposure and elimination of 5 gold/dendrimer composite nanodevices (CNDs) (5 nm positive, negative, and neutral, 11 nm negative, 22 nm positive) in mice using a physiologically based mathematical model. METHODS:400 ug of CNDs is injected intravenously to mice bearing melanoma cell line...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-012-0784-7

    authors： Mager DE,Mody V,Xu C,Forrest A,Lesniak WG,Nigavekar SS,Kariapper MT,Minc L,Khan MK,Balogh LP

    更新日期：2012-09-01 00:00:00

  • Permeation enhancer-containing water-in-oil nanoemulsions as carriers for intravesical cisplatin delivery.

    abstract：PURPOSE:In the present work, we developed water-in-oil (w/o) nanoemulsions for the intravesical administration of cisplatin. METHODS:The nanoemulsions were made up of soybean oil as the oil phase and Span 80, Tween 80, or Brij 98 as the emulsifier system. alpha-Terpineol and oleic acid were incorporated as permeation ...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-009-9947-6

    authors： Hwang TL,Fang CL,Chen CH,Fang JY

    更新日期：2009-10-01 00:00:00

  • The preparation and evaluation of a tablet dosage form of cyclosporine in dogs.

    abstract：:Cyclosporine (CsA) is commercially available for oral administration as a solution in olive oil with alcohol and an emulsifier. To improve its variable absorption and low patient acceptability, several oral formulations were prepared and tested in vitro and in vivo in dogs. A tablet formulation prepared by direct comp...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1015815614959

    authors： Abdallah HY,Mayersohn M

    更新日期：1991-04-01 00:00:00

  • Cellular uptake of cationic polymer-DNA complexes via caveolae plays a pivotal role in gene transfection in COS-7 cells.

    abstract：PURPOSE:Knowledge about the uptake mechanism and subsequent intracellular routing of non-viral gene delivery systems is important for the development of more efficient carriers. In this study we compared two established cationic polymers pDMAEMA and PEI with regard to their transfection efficiency and mechanism of cell...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-007-9287-3

    authors： van der Aa MA,Huth US,Häfele SY,Schubert R,Oosting RS,Mastrobattista E,Hennink WE,Peschka-Süss R,Koning GA,Crommelin DJ

    更新日期：2007-08-01 00:00:00

  • Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer.

    abstract：PURPOSE:Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40-42°C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. METHOD:Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-016-1971-8

    authors： Ranjan A,Benjamin CJ,Negussie AH,Chokshi S,Chung PH,Volkin D,Yeram N,Linehan WM,Dreher MR,Pinto PA,Wood BJ

    更新日期：2016-10-01 00:00:00

  • Structural interpretation in composite systems using powder X-ray diffraction: applications of error propagation to the pair distribution function.

    abstract：PURPOSE:To develop a method for drawing statistical inferences from differences between multiple experimental pair distribution function (PDF) transforms of powder X-ray diffraction (PXRD) data. METHODS:The appropriate treatment of initial PXRD error estimates using traditional error propagation algorithms was tested ...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-010-0259-7

    authors： Moore MD,Shi Z,Wildfong PL

    更新日期：2010-12-01 00:00:00

  • Moisture-induced aggregation of lyophilized DNA and its prevention.

    abstract：PURPOSE:To investigate the moisture-induced aggregation (i.e., a loss of solubility in water) of DNA in a solid state and to develop rational strategies for its prevention. METHODS:Lyophilized calf thymus DNA was exposed to relative humidity (RH) levels from 11% to 96% at 55 degrees C. Following a 24-h incubation unde...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-006-9138-7

    authors： Sharma VK,Klibanov AM

    更新日期：2007-01-01 00:00:00

  • Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by intestinal microorganisms.

    abstract：PURPOSE:We evaluated the effect of luminal bacterial metabolism on intestinal absorption of azetirelin in rats. In vitro characteristics of bacterial metabolism of azetirelin were also investigated with the goal of overcoming the low stability of the peptidic drug against luminal microorganisms. METHODS:Plasma azetire...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1012141025938

    authors： Sasaki I,Tamura T,Shibakawa T,Fujita T,Murakami M,Yamamoto A,Muranishi S

    更新日期：1997-08-01 00:00:00

  • Pulmonary delivery of deslorelin: large-porous PLGA particles and HPbetaCD complexes.

    abstract：PURPOSE:To compare the systemic delivery of deslorelin following intratracheal administration of different deslorelin formulations. The formulations included dry powders of deslorelin, large-porous deslorelin-poly(lactide-co-glycolide) (PLGA) particles, and small conventional deslorelin-PLGA particles. Also, solution f...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/b:pham.0000032997.96823.88

    authors： Koushik K,Dhanda DS,Cheruvu NP,Kompella UB

    更新日期：2004-07-01 00:00:00

  • Trimethyl chitosan-cysteine nanoparticles for systemic delivery of TNF-α siRNA via oral and intraperitoneal routes.

    abstract：PURPOSE:The lack of effective delivery vehicles impedes in vivo applications of siRNA. The trimethyl chitosan-cysteine (TC) nanoparticles (NPs) were developed for in vivo delivery of tumor necrosis factor α (TNF-α) siRNA via oral gavage and intraperitoneal injection. METHODS:The nanoparticles formulated from TC conjug...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-013-1086-4

    authors： He C,Yin L,Tang C,Yin C

    更新日期：2013-10-01 00:00:00

  • Differential contributions of rOat1 (Slc22a6) and rOat3 (Slc22a8) to the in vivo renal uptake of uremic toxins in rats.

    abstract：PURPOSE:Evidence suggests that uremic toxins such as hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS), and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) promote the progression of renal failure by damaging tubular cells via rat organic anion transporter 1 (rOat1) and rOat3 on the basolateral membrane of ...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-005-2486-x

    authors： Deguchi T,Kouno Y,Terasaki T,Takadate A,Otagiri M

    更新日期：2005-04-01 00:00:00

  • Structure in dehydrated trehalose dihydrate--evaluation of the concept of partial crystallinity.

    abstract：PURPOSE:(i) To use trehalose as a model compound to evaluate the concept of crystallinity in pharmaceuticals. (ii) To understand the structural nature of dehydrated trehalose dihydrate. MATERIALS AND METHODS:Trehalose dihydrate was dehydrated isothermally at several temperatures below 100 degrees C and the anhydrous p...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-006-9058-6

    authors： Rani M,Govindarajan R,Surana R,Suryanarayanan R

    更新日期：2006-10-01 00:00:00

  • In vitro and in vivo-release of nitroglycerin from a new transdermal therapeutic system.

    abstract：:A new transdermal therapeutic system (TTS) for nitroglycerin is presented that controls release of the active substance by means of desorption and diffusion. The drug release, in the dosage range examined under sink conditions, is independent of electrolytes and pH of the aqueous acceptor medium, but it does depend on...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/A:1016361921803

    authors： Wolff M,Cordes G,Luckow V

    更新日期：1985-01-01 00:00:00

  • Osmotic-driven release kinetics of bioactive therapeutic proteins from a biodegradable elastomer are linear, constant, similar, and adjustable.

    abstract：PURPOSE:The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial gro...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-006-9750-6

    authors： Gu F,Neufeld R,Amsden B

    更新日期：2006-04-01 00:00:00

  • In vivo evaluation of a colon-specific drug delivery system: an absorption study of theophylline from capsules coated with azo polymers in rats.

    abstract：:Azo polymers based upon 2-hydroxyethyl methacrylate, methyl methacrylate, and methacrylic acid, and containing N,N'-bis [(methacryloyloxyethyl)oxy(carbonylamino)]azobenzene as azo aromatic agent were evaluated in vivo as coating for colon-specific drug delivery. The gastrointestinal absorption of theophylline from cap...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1016283027139

    authors： Van den Mooter G,Samyn C,Kinget R

    更新日期：1995-02-01 00:00:00

  • Tissue distribution of indinavir administered as solid lipid nanocapsule formulation in mdr1a (+/+) and mdr1a (-/-) CF-1 mice.

    abstract：PURPOSE:Due to protease inhibitor (PI) efflux transport by P-glycoprotein (P-gp), insufficient PI concentrations result in low ongoing HIV replication in the so-called virus sanctuaries (brain and testes). The aim of the present study was to evaluate indinavir-loaded nanocapsules (Ind-LNC) including Solutol HS15, an ex...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-005-7147-6

    authors： Pereira de Oliveira M,Garcion E,Venisse N,Benoit JP,Couet W,Olivier JC

    更新日期：2005-11-01 00:00:00

  • Chitosan-based polyelectrolyte complexes as potential nanoparticulate carriers: physicochemical and biological characterization.

    abstract：PURPOSE:To investigate the effect of polyelectrolytes on the formation and physicochemical properties of chitosan nanoparticles (CS-NPs) used for the delivery of an anticancer drug, doxorubicin (DOX). METHOD:Three DOX-loaded CS-NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS-DS/DOX NPs),...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-013-1251-9

    authors： Ramasamy T,Tran TH,Cho HJ,Kim JH,Kim YI,Jeon JY,Choi HG,Yong CS,Kim JO

    更新日期：2014-05-01 00:00:00

  • Systemic administration of TerplexDNA system: pharmacokinetics and gene expression.

    abstract：PURPOSE:The aim of this study is to extend our previous studies to investigate the TerplexDNA synthetic gene carrier system in pharmacokinetics, biodistribution, and gene expression in major organs after systemic administration. METHODS:The stability of the TerplexDNA system was analyzed in vitro with a serum incubati...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1013081710135

    authors： Yu L,Suh H,Koh JJ,Kim SW

    更新日期：2001-09-01 00:00:00

  • Glycine crystallization during freezing: the effects of salt form, pH, and ionic strength.

    abstract：PURPOSE:The purpose of the study is to characterize glycine crystallization during freezing of aqueous solutions as a function of the glycine salt form (i.e., neutral glycine, glycine hydrochloride, and sodium glycinate), pH, and ionic strength. METHODS:Crystallization was studied by thermal analysis, microscopy, x-ra...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1016223101872

    authors： Akers MJ,Milton N,Byrn SR,Nail SL

    更新日期：1995-10-01 00:00:00

  • Effects of pluronic P85 on GLUT1 and MCT1 transporters in the blood-brain barrier.

    abstract：PURPOSE:The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess t...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/b:pham.0000048189.79606.6e

    authors： Batrakova EV,Zhang Y,Li Y,Li S,Vinogradov SV,Persidsky Y,Alakhov VY,Miller DW,Kabanov AV

    更新日期：2004-11-01 00:00:00

  • The metastatic stage-dependent mucosal expression of sialic acid is a potential marker for targeting colon cancer with cationic polymers.

    abstract：PURPOSE:Locoregional recurrence is the most common complication after adenocarcinoma resection in the colon, despite adjuvant chemotherapy. Therapy efficacy could be improved if designed to target malignant cells by incorporating specific recognition factors in the drugs or the drug vehicles. The aim of this study was ...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-007-9330-4

    authors： Azab AK,Kleinstern J,Srebnik M,Rubinstein A

    更新日期：2008-02-01 00:00:00

  • Intestinal absorption of miltefosine: contribution of passive paracellular transport.

    abstract：PURPOSE:This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS AND METHODS:Caco-2 cell monolayers were used as an in vitro model of...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-006-9170-7

    authors： Ménez C,Buyse M,Dugave C,Farinotti R,Barratt G

    更新日期：2007-03-01 00:00:00

  • Phase behavioral effects on particle formation processes using supercritical fluids.

    abstract：:The application of supercritical fluid (SF) processing in pharmaceutical research is increasing particularly in the field of particle formation for drug delivery systems. The SF processes have benefits over the existing particle formation methods in terms of improved control, flexibility and operational ease. This rev...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章,评审

    doi：10.1023/a:1011957512347

    authors： Palakodaty S,York P

    更新日期：1999-07-01 00:00:00

  • Heat-treated Fungizone retains amphotericin B antifungal activity without renal toxicity in rats infected with Aspergillus fumigatus.

    abstract：PURPOSE:The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus. METHODS:Infected rats were administered FZ and HFZ at a dosing regi...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/b:pham.0000041449.46054.b4

    authors： Sivak O,Bartlett K,Wasan KM

    更新日期：2004-09-01 00:00:00

  • Structural effects on the binding of amine drugs with the diphenylmethyl functionality to cyclodextrins. I. A microcalorimetric study.

    abstract：:Solution calorimetry has been employed to evaluate the stability constants and enthalpy changes associated with complex formation between alpha-, beta, or gamma-cyclodextrin (CD) and a group of amine compounds having the diphenylmethyl functionality. Data from thermal titrations of the compounds were analyzed using no...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1015880218535

    authors： Tong WQ,Lach JL,Chin TF,Guillory JK

    更新日期：1991-07-01 00:00:00

  • Hyaluronic Acid-Based Nanogels Produced by Microfluidics-Facilitated Self-Assembly Improves the Safety Profile of the Cationic Host Defense Peptide Novicidin.

    abstract：PURPOSE:Cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. Although potent and efficacious, systemic toxicity and low chemical stability have hampered their comme...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-015-1658-6

    authors： Water JJ,Kim Y,Maltesen MJ,Franzyk H,Foged C,Nielsen HM

    更新日期：2015-08-01 00:00:00

  • Dextran-catechin conjugate: a potential treatment against the pancreatic ductal adenocarcinoma.

    abstract：PURPOSE:A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC). METHODS:The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-012-0790-9

    authors： Vittorio O,Cirillo G,Iemma F,Di Turi G,Jacchetti E,Curcio M,Barbuti S,Funel N,Parisi OI,Puoci F,Picci N

    更新日期：2012-09-01 00:00:00

  • A new exact test for the evaluation of population pharmacokinetic and/or pharmacodynamic models using random projections.

    abstract：PURPOSE:Within-subject dependency of observations has a strong impact on the evaluation of population pharmacokinetic (PK) and/or pharmacodynamic (PD) models. To our knowledge, none of the current model evaluation tools correctly address this issue. We present a new method with a global test and easy diagnostic plot wh...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-011-0422-9

    authors： Laffont CM,Concordet D

    更新日期：2011-08-01 00:00:00

  • Insights into the role of electrostatic forces on the behavior of dry pharmaceutical particulate systems.

    abstract：PURPOSE:Under different charging conditions, particles can be either attracted or repulsed by each other, causing powder agglomeration or segregation. Such behavior can be detrimental in many processes aimed at achieving particulate mixture homogeneity. Consequently, the effects of electrostatic charges on mixing kinet...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1007/s11095-006-9934-0

    authors： Desrosiers Lachiver E,Abatzoglou N,Cartilier L,Simard JS

    更新日期：2006-05-01 00:00:00

  • Sequence alignments of the H(+)-dependent oligopeptide transporter family PTR: inferences on structure and function of the intestinal PET1 transporter.

    abstract：PURPOSE:To study the structure and function of the intestinal H+/ peptide transporter PET1, we compared its amino acid sequence with those of related transporters belonging to the oligopeptide transporter family PTR, and with more distant transporter families. METHODS:We have developed a new approach to the sequence a...

    journal_title：Pharmaceutical research

    pub_type： 杂志文章

    doi：10.1023/a:1012070726480

    authors： Graul RC,Sadée W

    更新日期：1997-04-01 00:00:00