Abstract：
PURPOSE:A mechanism-based PK-PD model was developed to predict the time course of dopamine D(2) receptor occupancy (D(2)RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. METHODS:A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of olanzapine in rats using the exposure (plasma and brain concentration) and D(2)RO profile obtained experimentally at various doses (0.01-40 mg/kg) administered by different routes. A two-compartment pharmacokinetic model was used to describe the plasma pharmacokinetic profile. A hybrid physiology- and mechanism-based model was developed to characterize the D(2) receptor binding in the striatum and was fitted sequentially to the data. The parameters were estimated using nonlinear mixed-effects modeling . RESULTS:Plasma, brain concentration profiles and time course of D(2)RO were well described by the model; validity of the proposed model is supported by good agreement between estimated association and dissociation rate constants and in vitro values from literature. CONCLUSION:This model includes both receptor binding kinetics and pharmacokinetics as the basis for the prediction of the D(2)RO in rats. Moreover, this modeling framework can be applied to scale the in vitro and preclinical information to clinical receptor occupancy.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Johnson M,Kozielska M,Pilla Reddy V,Vermeulen A,Li C,Grimwood S,de Greef R,Groothuis GM,Danhof M,Proost JHdoi
10.1007/s11095-011-0477-7subject
Has Abstractpub_date
2011-10-01 00:00:00pages
2490-504issue
10eissn
0724-8741issn
1573-904Xjournal_volume
28pub_type
杂志文章abstract：PURPOSE:The intratumoral heterogeneity observed in breast cancer (BC), in particular with regard to cell surface receptor expression, can hinder the success of many targeted cancer therapies. The development of novel therapeutic agents that target more than one receptor can overcome this inherent property of tumors and...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-019-2684-6
更新日期：2020-01-21 00:00:00
abstract：:A quantitative analysis of the dependence of dissolution rate on the relative surface area occupied by two non-interacting drug mixtures from co-compressed slabs is described. The results from the experimental dissolution rates of each component from naproxen/phenytoin co-compressed slabs under laminar flow conditions...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018979419714
更新日期：1994-10-01 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:Stable transformants expressing human multidrug resistance 1 (MDR1), monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b in LLC-PK1 were established to investigate species differences in P-glycoprotein (P-gp, ABCB1) mediated efflux activity. METHODS:The seven cDNAs of MDR1 from five an...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0285-7
更新日期：2006-07-01 00:00:00
abstract：PURPOSE:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016225707807
更新日期：1995-09-01 00:00:00
abstract：:A series of multilamellar liposome dispersions was prepared from lipids of soy phosphatidylcholine or hydrogenated soy phosphatidylcholine containing from 0 to 30 mol% of either cholesterol, stearylamine, or dipalmitoyl phosphatidylglycerol. The liposome dispersions were aerosolized with a Collison nebulizer for 80 mi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015924124180
更新日期：1990-11-01 00:00:00
abstract：:Since ancient times, natural products, herbs and spices have been used for preventing several diseases, including cancer. The term chemoprevention was coined in the late 1970s and referred to the prevention of cancer by selective use of phytochemicals or their analogs. The field utilizes experimental carcinogenesis mo...
journal_title：Pharmaceutical research
pub_type： 历史文章,杂志文章,评审
doi：10.1007/s11095-010-0085-y
更新日期：2010-06-01 00:00:00
abstract：PURPOSE:The objective of this study was to determine the influence of the peptide bond with emphasis on the carbonyl group on the interaction with and transport by the intestinal small-peptide carrier. Therefore enalapril, a known substrate for the small-peptide carrier, has been modified to an analogue with a reduced ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018866611555
更新日期：1999-01-01 00:00:00
abstract：PURPOSE:To develop a non-viral gene delivery system in the form of an oil-in-water (o/w) lipid emulsion. METHOD:Cationic lipid emulsions were formulated with soybean oil, 1,2-dioleoyl-sn-glycero-3-trimethylammonium-propane (DOTAP) as a cationic emulsifier and other co-emulsifiers. The physical characteristics of the l...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1007553106681
更新日期：2000-03-01 00:00:00
abstract：PURPOSE:We examined the ability of a protein transduction domain (PTD), YARA, to penetrate in the skin and carry a conjugated peptide, P20. The results with YARA were compared to those of a well-known PTD (TAT) and a control, nontransducing peptide (YKAc). The combined action of PTDs and lipid penetration enhancers was...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-2591-x
更新日期：2005-05-01 00:00:00
abstract：PURPOSE:PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein). METHODS:The insulin-phospholipid complex (INS-PLC) was prep...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-012-0944-9
更新日期：2013-04-01 00:00:00
abstract：:Seven healthy, male volunteers were entered into a randomized, open crossover study of the gastrointestinal transit of two enteric-coated 500-mg naproxen tablets. Two radiolabeled tablets were given to each volunteer on two occasions separated by 7 days, once in the fasted state and once after breakfast. Radiolabeling...
journal_title：Pharmaceutical research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1015858829187
更新日期：1992-11-01 00:00:00
abstract：PURPOSE:In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. METHODS:TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-009-9874-6
更新日期：2009-07-01 00:00:00
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
更新日期：2012-09-01 00:00:00
abstract：PURPOSE:This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. METHODS:25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1667-5
更新日期：2015-09-01 00:00:00
abstract：PURPOSE:To assess the effects of co-delivering osteoinductive DNA and/or small interfering RNA in directing the osteogenic differentiation of human adipose-derived stem cells (hADSCs) using a combinatorial, non-viral gene delivery approach. METHODS:hADSCs were transfected using combinations of the following genes: BMP...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-011-0406-9
更新日期：2011-06-01 00:00:00
abstract：PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/b:pham.0000029294.70707.74
更新日期：2004-06-01 00:00:00
abstract：PURPOSE:To investigate if gamma-Hydroxybutyrate (GHB) tolerance is mediated by alterations in GHB systemic pharmacokinetics, transport (blood brain barrier (BBB) and neuronal) or membrane fluidity. MATERIALS AND METHODS:GHB tolerance in rats was attained by repeated GHB administration (5.31 mmol/kg, s.c., QD for 5 day...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-9066-6
更新日期：2006-09-01 00:00:00
abstract：PURPOSE:Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant. METHODS:Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes s...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-018-2453-y
更新日期：2018-07-03 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：PURPOSE:Microphysiological systems (MPS), also known as "organs-on-chips" or "tissue chips," leverage recent advances in cell biology, tissue engineering, and microfabrication to create in vitro models of human organs and tissues. These systems offer promising solutions for modeling human physiology and disease in vitr...
journal_title：Pharmaceutical research
pub_type： 杂志文章,评审
doi：10.1007/s11095-019-2742-0
更新日期：2019-12-17 00:00:00
abstract：PURPOSE:To study epidermal and polyethylene membrane penetration and retention of the sunscreen benzophenone-3 (BP) from a range of single solvent vehicles and evaluate solvent effects on permeability parameters. METHODS:The solubility of BP was measured in a number of solvents. Penetration of BP across human epidermi...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011958006973
更新日期：1998-12-01 00:00:00
abstract：PURPOSE:Nonlinear conjugation metabolic rate of valproic acid (VPA) has been speculated previously from plasma elimination and liver concentration of VPA in guinea pigs. The purposes of the present study were to assess our speculation by direct measurement of VPA glucuronidation rate in vitro. METHODS:VPA at various c...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1016028707130
更新日期：1996-08-01 00:00:00
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
更新日期：2011-08-01 00:00:00
abstract：PURPOSE:The type and relative importance of saturated and unsaturated phospholipid components of surfactant within the epithelial lining fluid (ELF) of the inner and outer surfaces of the lung is not known. METHODS:Seven healthy dogs were anesthetized and a bronchoalveolar lavage (BAL) was performed, immediately follo...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-005-7677-y
更新日期：2005-11-01 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：:A method for determination of absorption rate and bioavailability was developed to reduce the influence of intraindividual variability and applied to the absolute intraperitoneal availability of lithium in the rat. In this method the test and the reference doses are given with a few hours' interval, and the resulting ...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1015939917646
更新日期：1989-09-01 00:00:00
abstract：PURPOSE:To develop an enzymatically-controlled pulsatile drug release system based on an impermeable capsule body, which contains the drug and is closed by an erodible pectin/pectinase-plug. METHODS:The plug was prepared by direct compression of pectin and pectinase in different ratios. In addition to the disintegrati...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1018959327311
更新日期：1999-09-01 00:00:00
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
更新日期：2015-08-01 00:00:00
abstract：PURPOSE:The objective of this work is to understand the sequence specificity of HAV peptides and to improve their selectivity in regulating E-cadherin-E-cadherin interactions in the intercellular junctions. METHODS:Peptide 1 was modified using an alanine scanning method to give peptides 2-6. The ability of these pepti...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1023/a:1011094025008
更新日期：2001-04-01 00:00:00
