Abstract：
:There have been no pharmacokinetic parameters and blood-brain equilibration rate constant (k e0) of propofol obtained in a single population of children, by which propofol can be administered using a target effect-site concentration controlled infusion. Thirty-nine, American Society of Anesthesiologists Physical Status 1-2 children aged 2-12 years were given an intravenous bolus of propofol (3 mg kg(-1)), followed by infusion (200 µg kg(-1) min(-1)). Arterial drug concentrations and bispectral index (BIS) values were measured. Population pharmacokinetic and pharmacodynamic analysis was performed using nonlinear mixed effects modeling. External model validation was performed in a separate population of children. A two-compartment model and a sigmoid E max model directly linked by an effect compartment well described the time courses of propofol concentration and BIS. The estimates of parameters were: V 1 (L) = 1.69, V 2 (L) = 27.2 + 0.929 × (weight - 25), Cl (L min(-1)) = 0.893 × (weight/23.6)(0.966), Q (L min(-1)) = 1.3; E 0 = 76.9; E max = 35.4, Ce 50 (μg mL(-1)) = 3.47 - (0.095 × age) - (1.63 × mean infusion rate of remifentanil in µg kg(-1) min(-1)); γ = 2.1; and k e0 (min(-1)) = 0.371. Pooled biases (95 % CI) of the target effect-site concentration controlled infusion system of propofol was -20.2 % (-23.3 to -18.1 %) and pooled inaccuracy was 30.4 % (28.6-32.7 %). Pooled biases of BIS prediction was -6.8 % (-9.1 to -4.1 %) and pooled inaccuracies was 19.1 % (17.5-20.9 %).The altered weight-based dose requirements of propofol are well described pharmacokinetically, and pharmacodynamically. Predictive performances of the TCI system in this study were clinically acceptable.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Choi BM,Lee HG,Byon HJ,Lee SH,Lee EK,Kim HS,Noh GJdoi
10.1007/s10928-015-9408-2subject
Has Abstractpub_date
2015-04-01 00:00:00pages
163-77issue
2eissn
1567-567Xissn
1573-8744journal_volume
42pub_type
杂志文章abstract：:A retrospective analysis was performed to modify our fourth-generation pharmacodynamic model for glucocorticoid receptor (GR) dynamics with incorporation of more physiological features. This modified model was developed by integrating previously reported free cytosolic GR and GR mRNA data following single (10, 50 mg/k...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-007-9049-1
更新日期：2007-06-01 00:00:00
abstract：:Age-structured cell population model was introduced to describe cell survival. The impact of the environment on the cell population is represented by drug plasma concentration. A key model variable is the hazard of cell removal that is a subject to the environment effect. The model is capable of describing cohort and ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-017-9520-6
更新日期：2017-08-01 00:00:00
abstract：:Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to int...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-012-9243-7
更新日期：2012-04-01 00:00:00
abstract：:3-hydroxybenzo(a)pyrene (3-OHBaP) in urine has been proposed as a biomarker of occupational exposure to polycyclic aromatic hydrocarbons. However, to reconstruct exposure doses in workers from biomarker measurements, a thorough knowledge of the kinetics of the benzo(a)pyrene (BaP) and 3-OHBaP given different routes of...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-013-9338-9
更新日期：2013-12-01 00:00:00
abstract：:The physiologically based pharmacokinetic (PBPK) models allow for predictive assessment of variability in population of interest. One of the future application of PBPK modeling is in the field of precision dosing and personalized medicine. The aim of the study was to develop PBPK model for amitriptyline given orally, ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-018-9597-6
更新日期：2018-10-01 00:00:00
abstract：:We propose an efficient algorithm for screening covariates in population model building using Wald's approximation to the likelihood ratio test (LRT) statistic in conjunction with Schwarz's Bayesian criterion. The algorithm can be applied to a full model fit of k covariate parameters to calculate the approximate LRT f...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1023/a:1011579109640
更新日期：2001-06-01 00:00:00
abstract：:There are situations in drug development where one may wish to reduce the dimensionality and complexity of whole body physiologically based pharmacokinetic models. A technique for formal reduction of such models, based on global sensitivity analysis, is suggested. Using this approach mean and variance of tissue(s) and...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-005-0004-8
更新日期：2006-02-01 00:00:00
abstract：:The objective was to develop a physiologically-based pharmacokinetic (PBPK) model to characterize the whole-body disposition of paclitaxel (formulated in Cremophor EL and ethanol-Taxol®) in mice and to evaluate the utility of this model for predicting pharmacokinetics in other species. Published studies that reported ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-018-9586-9
更新日期：2018-08-01 00:00:00
abstract：:Optimizing designs using robust (global) optimality criteria has been shown to be a more flexible approach compared to using local optimality criteria. Additionally, model based adaptive optimal design (MBAOD) may be less sensitive to misspecification in the prior information available at the design stage. In this wor...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-017-9521-5
更新日期：2017-08-01 00:00:00
abstract：:HER2-positive breast cancer (BC) is a rapidly growing and aggressive BC subtype that predominantly affects younger women. Despite improvements in patient outcomes with anti-HER2 therapy, primary and/or acquired resistance remain a major clinical challenge. Here, we sought to use a quantitative systems pharmacological ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-020-09732-x
更新日期：2021-01-03 00:00:00
abstract：:Current physiologically based pharmacokinetic (PBPK) models are inductive. We present an additional, different approach that is based on the synthetic rather than the inductive approach to modeling and simulation. It relies on object-oriented programming. A model of the referent system in its experimental context is s...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-006-9031-3
更新日期：2006-12-01 00:00:00
abstract：:Long term therapy with antiretroviral agents in HIV-infected patients often result in failure to suppress the virus load. Imperfect adherence to prescribed antiviral drugs is an important factor explaining the resurgence of virus. A better understanding of the factors responsible for the virological failure is importa...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-006-9022-4
更新日期：2006-08-01 00:00:00
abstract：:Tocilizumab is a recombinant humanized antihuman interleukin-6 receptor monoclonal antibody, which inhibits binding of IL-6 to its soluble (sIL-6R) and membrane-expressed (mIL-6R) receptors. The work investigated whether the observed decline in peripheral neutrophil and platelet counts after tocilizumab administration...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10928-011-9227-z
更新日期：2012-02-01 00:00:00
abstract：:During the course of therapeutic drug monitoring (TDM), doses are adjusted to attain a target concentration range and a correlation between clearance (CL) and dose is introduced. In population pharmacokinetic analyses of such TDM data, CL has frequently been modeled as a function of dose. This paper demonstrates by si...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-005-0083-6
更新日期：2005-12-01 00:00:00
abstract：:A number of experimental observations in the late 1960s, early 1970s could not be explained by the pharmacokinetic theory available at that time. For example rats receiving phenobarbital as an enzyme inducing agent exhibited increased elimination of phenylbutazone in vitro in liver microsomes and in vivo in whole anim...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章,评审
doi：10.1007/s10928-010-9187-8
更新日期：2010-12-01 00:00:00
abstract：:Target-mediated drug disposition (TMDD) is frequently reported for therapeutic monoclonal antibodies and is linked to the high affinity and high specificity of antibody molecules for their target. Understanding TMDD of a monoclonal antibody should go beyond the empirical description of its non-linear PK since valuable...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章,评审
doi：10.1007/s10928-009-9129-5
更新日期：2009-10-01 00:00:00
abstract：:T cell responses are a crucial part of the adaptive immune system in the fight against infections. This article discusses the use of mathematical models for understanding the dynamics of cytotoxic T lymphocyte (CTL) responses against viral infections. Complementing experimental research, mathematical models have been ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章,评审
doi：10.1007/s10928-014-9387-8
更新日期：2014-10-01 00:00:00
abstract：:This study aimed to characterize pharmacodynamic interaction between propofol and aminophylline. Nine beagle dogs were randomly allocated at the propofol rates of 0.75 (group A), 1.00 (group B), and 1.25 (group C) mg/kg/min. During period 1, propofol only was infused, while during period 2, aminophylline only, at the ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-014-9377-x
更新日期：2014-12-01 00:00:00
abstract：:Mathematical modeling of drug effects maximizes the information gained from an experiment, provides further insight into the mechanisms of drug effects, and allows for simulations in order to design studies or even to derive clinical treatment strategies. We reviewed modeling of antimicrobial drug effects and show tha...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章,评审
doi：10.1007/s10928-007-9069-x
更新日期：2007-12-01 00:00:00
abstract：:Mixture models are applied in population pharmacometrics to characterize underlying population distributions that are not adequately approximated by a single normal or lognormal distribution. In addition to obtaining individualized maximum a posteriori Bayesian post hoc parameter estimates, the subpopulation to which ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 临床试验,杂志文章
doi：10.1007/s10928-006-9038-9
更新日期：2007-04-01 00:00:00
abstract：:This study was designed to investigate the pharmacokinetics/pharmacodynamics (PK/PD) risk factors preceding the onset of type 2 diabetes using a population-based Bayesian nonlinear hierarchical model to describe the glucose-insulin kinetics. One hundred fifty-two healthy subjects with a family history of type 2 diabet...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-009-9130-z
更新日期：2009-10-01 00:00:00
abstract：:The majority of measures proposed to date for direct curve comparison in bioequivalence studies were investigated. These measures have often been called metrics, but in most cases this was incorrect in the mathematical sense. It was demonstrated, with a set of counter-examples, that the axioms of a metric are fulfille...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-009-9121-0
更新日期：2009-06-01 00:00:00
abstract：:The aim of this study was to develop a population in vitro-in vivo pharmacokinetic model that simultaneously describe the absorption and accumulation kinetics of itraconazole (ICZ) and hydroxy-itraconazole (HICZ) in healthy subjects. The model integrated meta-models of gastrointestinal pH and gastrointestinal transit ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-017-9555-8
更新日期：2018-04-01 00:00:00
abstract：:The utilisation of physiologically-based pharmacokinetic models for the analysis of population data is an approach with progressively increasing impact. However, as we move from empirical to complex mechanistic model structures, incorporation of stochastic variability in model parameters can be challenging due to the ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-015-9418-0
更新日期：2015-08-01 00:00:00
abstract：:Assessment of the elimination of an oral test dose based on plasma concentration values requires correction for the effect of gastric release and absorption. Irregular uptake processes should be described 'model independently', which requires estimation of a large number of absorption parameters. To limit the associat...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-013-9299-z
更新日期：2013-04-01 00:00:00
abstract：:The purpose of this study was to develop a whole-body physiologically based pharmacokinetic (WB-PBPK) model for ciprofloxacin for ICU patients, based on only plasma concentration data. In a next step, tissue and organ concentration time profiles in patients were predicted using the developed model. The WB-PBPK model w...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-016-9486-9
更新日期：2017-04-01 00:00:00
abstract：:The purpose of this study was to evaluate whether mixed effects modeling (MEM) performs better than either noncompartmental or compartmental naïve pooled data (NPD) analysis for the interpretation of single sample per subject pharmacokinetic (PK) data. Using PK parameters determined during a toxicokinetic study in rat...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1023/a:1011507100493
更新日期：2001-04-01 00:00:00
abstract：:Guselkumab, a human IgG1 monoclonal antibody that blocks interleukin-23, has been evaluated in one Phase 2 and two Phase 3 trials in patients with moderate-to-severe psoriasis, in which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Investigator's Global Assessment (IGA) scores. Throu...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-018-9581-1
更新日期：2018-08-01 00:00:00
abstract：:Development of novel therapies for bone diseases can benefit from mathematical models that predict drug effect on bone remodeling biomarkers. Therefore, a bone cycle model (BCM) was developed that takes into consideration the concept of the basic multicellular unit and the dynamic equilibrium of bone remodeling. The m...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-015-9423-3
更新日期：2015-08-01 00:00:00
abstract：:Neutropenia is a common side-effect of oncology drugs. We aimed to study the impact of exposure and dosing schedule on neutropenia to guide selection of dosing schedules that minimize neutropenia potential while maintaining the desired minimum concentration (Cmin) required for target engagement. Dose, frequency and PK...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-019-09667-y
更新日期：2020-02-01 00:00:00
