Abstract：
:Pharmacokinetic/pharmacodynamic (PK/PD)-modeling links dose-concentration relationships (PK) and concentration-effect relationships (PD), thereby facilitating the description and prediction of the time course of drug effects resulting from a certain dosing regimen. PK/PD-modeling approaches can basically be distinguished by four major attributes. The first characterizes the link between measured drug concentration and the response system, direct link versus indirect link. The second considers how the response system relates effect site concentration to the observed outcome, direct versus indirect response. The third regards what clinically or experimentally assessed information is used to establish the link between concentration and effect, hard link versus soft link. And the fourth considers the time dependency of pharmacodynamic model parameters, distinguishing between time-variant versus time-invariant. Application of PK/PD-modeling concepts has been identified as potentially beneficial in all phases of preclinical and clinical drug development. Although today predominantly limited to research, broader application of PK/PD-concepts in clinical therapy will provide a more rational basis for patient-specific dosage individualization and may thus guide applied pharmacotherapy to a higher level of performance.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Derendorf H,Meibohm Bdoi
10.1023/a:1011907920641subject
Has Abstractpub_date
1999-02-01 00:00:00pages
176-85issue
2eissn
0724-8741issn
1573-904Xjournal_volume
16pub_type
杂志文章abstract：:(+)-Propranolol was infused at two rates into the pyloric vein (a portal vein tributary) of 15 male Sprague Dawley rats until apparent steady-state conditions were established (i.e., 8 hr at each rate). One group (n = 7) received the high dose (40 micrograms/min/kg) first, and in the other group (n = 8) the low dose (...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018921306200
更新日期：1994-03-01 00:00:00
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
更新日期：2016-10-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate the depth-dependent intradermal immunogenicity of inactivated polio vaccine (IPV) delivered by depth-controlled microinjections via hollow microneedles (HMN) and to investigate antibody response enhancing effects of IPV immunization adjuvanted with CpG oligodeoxynucleoti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1965-6
更新日期：2016-09-01 00:00:00
abstract：PURPOSE:Hydroxylation of the antidepressant and smoking deterrent drug bupropion is a clinically important bioactivation and elimination pathway. Bupropion hydroxylation is catalyzed selectively by cytochrome P4502B6 (CYP2B6). CYP2B6-catalyzed bupropion hydroxylation has been used as an in vitro and in vivo phenotypic ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-008-9535-1
更新日期：2008-06-01 00:00:00
abstract：PURPOSE:Excipients are added to lyophilized protein drug formulations to protect the protein during processing and storage, but the mechanisms are poorly understood. Here, hydrogen/deuterium (H/D) exchange with mass spectrometry was used to assess protein conformation and excipient interactions in lyophilized solids. ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-007-9365-6
更新日期：2008-02-01 00:00:00
abstract：PURPOSE:Information on genetic variants that affect the pharmacokinetics and pharmacodynamics (PK/PD) of drugs in different populations from Mexico is still an ongoing endeavor. Here, we investigate allele frequencies on pharmacogenetic targets in Mexican Mestizos and Natives from three different States and its associa...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-016-1990-5
更新日期：2016-11-01 00:00:00
abstract：PURPOSE:A rapid immune response is required to prevent death from Anthrax, caused by Bacillus anthracis. METHOD:We formulated a vaccine carrier comprised of acetalated dextran microparticles encapsulating recombinant protective antigen (rPA) and resiquimod (a toll-like receptor 7/8 agonist). RESULTS:We were able to p...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-0975-x
更新日期：2013-05-01 00:00:00
abstract：PURPOSE:To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders. METHODS:From a dry powder a fraction of aerosolized particles with an aerodynamic particle size below 5 μm was collected on regenerate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0744-2
更新日期：2012-08-01 00:00:00
abstract：:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addresse...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-007-9431-0
更新日期：2008-03-01 00:00:00
abstract：:The hair follicle, hair shaft, and sebaceous gland collectively form what is recognized as the pilosebaceous unit. This complex, three-dimensional structure within the skin possesses a unique biochemistry, metabolism and immunology. Recent studies have focused on the hair follicle as a potential pathway for both local...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1023/a:1016250422596
更新日期：1995-02-01 00:00:00
abstract：PURPOSE:To develop a new technique, spray freeze drying, for preparing protein aerosol powders. Also, to compare the spray freeze-dried powders with spray-dried powders in terms of physical properties and aerosol performance. METHODS:Protein powders were characterized using particle size analysis, thermogravimetric an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018828425184
更新日期：1999-02-01 00:00:00
abstract：:The possible mechanism of hepatic uptake of colchicine (CLC), a microtubule system disrupting agent, was examined using isolated rat hepatocytes. The existence of a carrier-mediated active transport system for CLC was demonstrated. This transport system is saturable, is affected by metabolic inhibitors (dinitrophenol,...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015917601349
更新日期：1989-03-01 00:00:00
abstract：PURPOSE:TXA9, a novel cardiac glycoside, has a potent anti-proliferative effect against A549 human lung cancer cells, however, possesses a poor water-solubility and a rapid metabolic rate in vivo which limited the further development of TXA9. To overcome the shortcomings of TXA9, four polymer prodrugs of TXA9 were desi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-020-02789-w
更新日期：2020-03-12 00:00:00
abstract：:The transepithelial transport of arginine vasopressin (AVP) across cultured rat alveolar epithelial cell monolayers was studied. At 0.1 nM donor [125I]AVP, the radiolabel flux measured in the apical-to-basolateral (AB) direction was about 10 times greater than that in the reverse (BA) direction. HPLC analyses of the b...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018918022865
更新日期：1994-11-01 00:00:00
abstract：PURPOSE:To develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA). METHODS:Synthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coate...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2177-4
更新日期：2017-08-01 00:00:00
abstract：:The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sig...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015880327911
更新日期：1992-07-01 00:00:00
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 th...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016031129053
更新日期：1996-05-01 00:00:00
abstract：:We describe a simplified and rapid liquid chromatographic determination of antipyrine clearance (CLAP) calculated from peak height ratios of drug/internal standard. Saliva or plasma was collected 24 hr after the oral administration of 1 g of antipyrine to the subject. A 25-microliter aliquot of the sample is deprotein...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015816825920
更新日期：1991-02-01 00:00:00
abstract：:Biotherapeutics, including recombinant or plasma-derived human proteins and antibody-based molecules, have emerged as an important class of pharmaceuticals. Aggregation and immunogenicity are among the major bottlenecks during discovery and development of biotherapeutics. Computational tools that can predict aggregati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0414-9
更新日期：2011-05-01 00:00:00
abstract：:The effects of process and storage conditions of solid-state emulsions were studied. Oil-in-water emulsions may be prepared from solid state emulsions by adding an aqueous phase to the solid. Solid-state emulsions are prepared by processing an oil phase and an aqueous solution of matrix material via a solvent removal ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018983227234
更新日期：1993-07-01 00:00:00
abstract：PURPOSE:The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. METHODS:Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9568-2
更新日期：2006-03-01 00:00:00
abstract：PURPOSE:Proteasome inhibition induces endoplasmic reticulum (ER) stress and compensatory autophagy to relieve ER stress. Disturbance of intracellular calcium homeostasis can lead to ER stress and alter the autophagy process. It has been suggested that inhibition of the proteasome disrupts intracellular calcium homeosta...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-013-1139-8
更新日期：2013-09-01 00:00:00
abstract：PURPOSE:Anticancer chemotherapy usually involves the administration of several anticancer drugs that differ in their action mechanisms. Here, we aimed to test whether the combination of omacetaxine mepesuccinate (OMT) and doxorubicin (DOX) could show synergism, and whether the liposomal co-delivery of these two drugs c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1317-3
更新日期：2014-08-01 00:00:00
abstract：:Various carboxylic acid esters of the N-hydroxymethyl derivative of N-benzyloxycarbonylglycine benzylamide, used as a peptide-like model, were prepared and their decomposition kinetics studied in aqueous solution and in human plasma solutions. These N-acyloxymethylamide derivatives were found to undergo a facile decom...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015839426229
更新日期：1991-10-01 00:00:00
abstract：PURPOSE:To measure aggregate and particle formation in tumor necrosis factor-alpha (TNF-α) inhibitors etanercept, adalimumab and certolizumab pegol product samples after exposure to freezing temperature conditions similar to storage conditions previously observed in patients' homes. METHODS:TNF-α inhibitors in their o...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-017-2341-x
更新日期：2018-02-05 00:00:00
abstract：PURPOSE:The blood-brain barrier (BBB) essentially restricts therapeutic drugs from entering into the brain. This study tests the hypothesis that brain endothelial cell derived exosomes can deliver anticancer drug across the BBB for the treatment of brain cancer in a zebrafish (Danio rerio) model. MATERIALS AND METHODS...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-014-1593-y
更新日期：2015-06-01 00:00:00
abstract：:Effects of protease inhibitors and absorption enhancers on the absorption of salmon calcitonin (sCT) were evaluated after intratracheal coadministration to rats using the plasma Ca level as an index. Remarkable absorption enhancement could be attained with unsaturated fatty acids such as oleic acid and polyoxyethylene...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018926007902
更新日期：1994-09-01 00:00:00
abstract：PURPOSE:The purpose of this study was to characterize the amorphous state of ursodeoxycholic acid (UDCA) samples by using isothermal microcalorimetry, X-ray diffraction, infrared (IR) spectroscopy and solid state carbon 13 nuclear magnetic resonance (13C-NMR) spectroscopy, and to demonstrate the application of the ther...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1012114825513
更新日期：1997-06-01 00:00:00
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
更新日期：2001-09-01 00:00:00
abstract：PURPOSE:To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. METHODS:Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0830-5
更新日期：2012-12-01 00:00:00
