Abstract:
:The application of microdialysis technique for the investigation of pharmacokinetics and pharmacodynamics of drugs requires careful assessment of probe performance to ensure validity of the data obtained using this technique. The aim of this study was to establish and validate the microdialysis technique for investigation of the pharmacokinetics and pharmacodynamics of the neuromuscular blocker, gallamine. In vitro recovery of gallamine from the microdialysis probe when different perfusion flow rates were employed was evaluated leading to selection of a flow rate of 2 microl/min with 15-min sampling intervals for the subsequent studies. In vitro recovery of gallamine from the microdialysis probe was independent of concentration, stable over an 8-h period and reproducible. Comparable in vitro recoveries were obtained by different established approaches including recovery estimation by gain, loss and the zero-net flux (ZNF) method. Recovery by loss was used to study the in vivo recovery of gallamine from rat muscle tissue. The in vivo recovery was stable over a 5.5-h sampling period. In vitro performance of the probe subsequent to the in vivo study remained stable supporting reusage of the probe. These data highlight the importance of a systematic examination of microdialysis probe validation.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Sasongko L,Williams KM,Ramzan I,McLachlan AJdoi
10.1016/s1056-8719(00)00117-9keywords:
subject
Has Abstractpub_date
2000-11-01 00:00:00pages
519-25issue
3eissn
1056-8719issn
1873-488Xpii
S1056-8719(00)00117-9journal_volume
44pub_type
杂志文章abstract:INTRODUCTION:The ability to quantify systemic concentrations of protein therapeutics is complicated by the presence of endogenous analyte, specific binding proteins, and nonspecific matrix components in biological matrices (Lee & Ma, 2007). Further complications can be introduced following pegylation whereby polyethyle...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.12.004
更新日期:2010-03-01 00:00:00
abstract::Lipid peroxidation is a major consequence of oxidative stress and an important cause of neuronal damage in ischaemic injuries and neurodegenerative disorders such as Parkinson's disease. Recent research has focused on the development of antioxidant drugs which may delay or minimize neurodegeneration. Rapid and reliabl...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(98)00022-7
更新日期:1998-04-01 00:00:00
abstract::A method for determination of cis-diaminedichloroplatinum (II) (cisplatin) in ultrafiltered plasma, cell, and tumour samples is described. Cisplatin separation was carried out on a reversed-phase column using methanol-acetonitrile-water as the mobile phase. The flow rate was maintained constant at 1.6 mL/min and analy...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.06.005
更新日期:2005-11-01 00:00:00
abstract:INTRODUCTION:There has been an increasing need to conduct investigative safety pharmacology studies to complement regulatory-required studies, particularly as it applies to a comprehensive assessment of cardiovascular (CV) risk. METHODS:We describe refined methodology using a combination of telemetry and direct signal...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2016.05.002
更新日期:2016-09-01 00:00:00
abstract::The Safety Pharmacology Society organized a scientific session at its annual conference in 2017 to discuss the challenges and opportunities of the Comprehensive In-Vitro Proarrhythmia Assay (CiPA) paradigm. Our intention was to raise awareness of this initiative with its members and also to gauge the extent to which s...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,评审
doi:10.1016/j.vascn.2018.06.005
更新日期:2018-01-01 00:00:00
abstract::The most commonly employed techniques for the in vivo measurement of arterial blood flow to individual organs involve the use of flow probes or sensors. Commercially available systems for the measurement of in vivo blood flow can be divided into two categories: ultrasonic and electromagnetic. Two types of ultrasonic p...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,评审
doi:10.1016/s1056-8719(00)00123-4
更新日期:2000-09-01 00:00:00
abstract:INTRODUCTION:The analytical solutions to compartmental pharmacokinetic models are well known, but have not been presented in a form that easily allows for complex dosing regimen and changes in covariate/parameter values that may occur at discrete times within and/or between dosing intervals. METHODS:Laplace transforms...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2015.03.004
更新日期:2015-05-01 00:00:00
abstract:INTRODUCTION:Terfenadine, cisapride, and E-4031, three drugs that prolong ventricular repolarization, were selected to evaluate the sensitivity of the conscious chronic atrioventricular node--ablated, His bundle-paced Dog for defining drug induced cardiac repolarization prolongation. A novel predictive pharmacokinetic/...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.02.003
更新日期:2006-01-01 00:00:00
abstract:INTRODUCTION:Simultaneous recording of electrical potentials from multiple cells may be useful for physiological and pharmacological research. The present study aimed to establish an in vitro cardiac hypoxia experimental platform on the microelectrode array (MEA). METHODS:Embryonic rat cardiac myocytes were cultured o...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.02.005
更新日期:2009-05-01 00:00:00
abstract::The properties of the ternary complex model (TCM) of drug action at G protein-coupled receptors (GPCRs) were examined, using theoretical computer simulations, with regard to the predicted effects of the presence of a fixed concentration of one agonist on the competition binding profile of another. Subsequently, the bi...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(00)00078-2
更新日期:2000-01-01 00:00:00
abstract::Investigations of the coupling between contraction and relaxation (contraction-relaxation [CRC] process) in isometric conditions are essential in determining whether pharmacologic interventions or cardiac diseases specifically modify isometric relaxation (intrinsic lusitropic effect) or change it in proportion with th...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(99)00044-1
更新日期:1999-09-01 00:00:00
abstract::This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2016 Safety Pharmacology Society (SPS), Canadian Society of Pharmacology and Therapeutics (CSPT), and J...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 社论
doi:10.1016/j.vascn.2017.04.012
更新日期:2017-09-01 00:00:00
abstract::High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g., Oct-4) prior to HCS, which can be time consuming and labor intensive. In this study, we employed transgenic hESC...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106913
更新日期:2020-01-01 00:00:00
abstract::The purpose of this study was to develop a simple and noninvasive method for the quantitative evaluation of neuromuscular blockade in mice. The sciatic nerve in anesthetized animals (etomidate, 50 mg/kg or mephenesin, 250 mg/kg) was stimulated using transcutaneous electrodes; repetitive supramaximal stimulations (3 Hz...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(92)90033-w
更新日期:1992-05-01 00:00:00
abstract:INDUCTION:Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models re...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2020.106892
更新日期:2020-09-01 00:00:00
abstract::The aim of the present study was to formulate a simple chemically defined medium for the in vitro growth of rat two-cell embryos to blastocysts. Embryos from day 2 pregnant rats were retrieved and placed in paraffin oil-covered droplets of "rat two-cell embryo culture medium" (R2ECM) containing combinations of various...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(00)00084-8
更新日期:2000-05-01 00:00:00
abstract::The use of animal models is an essential part of medical research and drug development. The essential skills required to be able to do such research includes experimental design, statistical analysis and the actual handling and treating of the animals (in vivo skills). The number of students in the U.K. receiving trai...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2011.07.002
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:Detection of drug effects on neuronal synapses is important for predicting their adverse effects. We have used drebrin as a marker to detect the synaptic changes in cultured neurons. High concentration of glutamate decreases the amount of drebrin in synapses. To increase the availability of this method for...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2019.106607
更新日期:2019-01-01 00:00:00
abstract::Recently, Calderone and Martinotti (J Pharmacol Toxicol Meth 40:57-62, 1998) presented a simple equation for the estimation of agonist dissociation equilibrium constants from data obtained from receptor inactivation experiments using an irreversible, competitive antagonist. In the present paper, however, it is demonst...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(99)00011-8
更新日期:1998-11-01 00:00:00
abstract::Chronic use of beta2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of beta-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo mo...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(98)00046-x
更新日期:1998-08-01 00:00:00
abstract:INTRODUCTION:Increase of serum alanine aminotransferase (ALT) activity is widely used as a surrogate marker for tissue damage. Two ALT isoforms, ALT1 and ALT2, have been cloned recently in mammals. The study investigated the source of elevated ALT activity in serum of dogs treated with a hepatotoxic compound. METHODS:...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.09.001
更新日期:2009-11-01 00:00:00
abstract:INTRODUCTION:Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maint...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,多中心研究
doi:10.1016/j.vascn.2013.04.008
更新日期:2013-07-01 00:00:00
abstract::Induction of acute myocardial infarction in the rat is an established model for studying effects of therapeutic interventions. Images of sections of the rat left ventricle, stained with nitroblue tetrazolium, were digitized and several parameters estimated by dedicated software on an image analyzer (IBAS 2.0). The met...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(95)00019-e
更新日期:1995-08-01 00:00:00
abstract:INTRODUCTION:The quantification of [(3)H]noradrenaline spillover from electrically stimulated, sympathetic nerves is a widely used method to study presynaptic effects of hormones, transmitters and drugs. Although a straightforward approach, the execution of the experiments is not trivial. This holds true mainly for a r...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(02)00170-3
更新日期:2001-11-01 00:00:00
abstract::The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animal...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.12.003
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Accurate preclinical modeling of diabetic complications such as retinopathy, nephropathy and neuropathy is crucial to enable the development of novel preventative therapies. The aims of this study were to establish a model of long-term diabetes with sustained medium scale hyperglycemia and characterize the...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2015.11.003
更新日期:2016-03-01 00:00:00
abstract::A radioimmunoassay of the undecapeptide substance P (SP) and its application in rabbit lung superfusate has been developed. The assay was based on the use of a radioactive tracer, 125I-SP-Tyr8, which showed, with an excess of antibodies, a specific binding greater than 90% and a nonspecific binding lower than 2%. This...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(98)00012-4
更新日期:1998-03-01 00:00:00
abstract:INTRODUCTION:The purpose of this study was to evaluate the feasibility of using gel electrophoresis combined with autoradiographic image analysis for quantitating protein drug concentrations in biological fluid for pharmacokinetic studies. METHODS:Protein drugs were iodinated using the Iodogen reagent and injected int...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(02)00203-4
更新日期:2002-01-01 00:00:00
abstract:INTRODUCTION:RL-14 cells, human fetal ventricular cardiomyocytes, are a commercially available cell line that has been established from non-proliferating primary cultures derived from human fetal heart tissue. However, the expression of different drug metabolizing enzymes (DMEs) in RL-14 cells has not been elucidated y...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.11.005
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Gastrointestinal (GI) motility disorders include many clinical manifestations associated with various pathologies. They are widespread and can be considered a primary symptom or can be associated to other diseases, such as Parkinson's disease. Understanding the type and site of GI dysmotility is crucial to...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.08.003
更新日期:2014-09-01 00:00:00