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 associated computational effort a new approach is developed with a reduced number of unknown parameters. A marginalized and regularized absorption approach (MRA) is defined, which uses for the uptake just one parameter to control rigidity of the uptake curve. For validation, elimination and absorption were reproduced using published IVIVC data and a synthetic data set for comparison with approaches using a 'model-free'--staircase function or mechanistic models to describe absorption. MRA performed almost as accurate as well specified mechanistic models, which gave the best reproduction. MRA demonstrated a 50fold increase in computational efficiency compared to other approaches. The absorption estimated for the IVIVC study demonstrated an in vivo-in vitro correlation comparable to published values. The newly developed MRA approach can be used to efficiently and accurately estimate elimination and absorption with a restricted number of adaptive parameters and with automatic adjustment of the complexity of the uptake.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Vogt JA,Denzer Cdoi
10.1007/s10928-013-9299-zsubject
Has Abstractpub_date
2013-04-01 00:00:00pages
177-87issue
2eissn
1567-567Xissn
1573-8744journal_volume
40pub_type
杂志文章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::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::Ordinary differential equation models often contain a large number of parameters that must be determined from measurements by estimation procedure. For an estimation to be successful there must be a unique set of parameters that can have produced the measured data. This is not the case if a model is not structurally i...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-019-09624-9
更新日期:2019-04-01 00:00:00
abstract::To solve the problem of estimating an unknown input function to a linear time invariant system we propose an adaptive non-parametric method based on reversible jump Markov chain Monte Carlo (RJMCMC). We use piecewise polynomial functions (splines) to represent the input function. The RJMCMC algorithm allows the explor...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-006-9045-x
更新日期:2007-06-01 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::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::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::Bridging fundamental approaches to model optimization for pharmacometricians, systems pharmacologists and statisticians is a critical issue. These fields rely primarily on Maximum Likelihood and Extended Least Squares metrics with iterative estimation of parameters. Our research combines adaptive chaos synchronization...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-019-09629-4
更新日期:2019-04-01 00:00:00
abstract::Quantitative systems pharmacology (QSP) is a recent addition to the modeling and simulation toolbox for drug discovery and development and is based upon mathematical modeling of biophysical realistic biological processes in the disease area of interest. The combination of preclinical neurophysiology information with c...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-013-9297-1
更新日期:2013-06-01 00:00:00
abstract::Changes in the reticulocyte subtype distribution (high, medium and low reticulocytes count (HR, MR, LR)) measured by flow cytometry following phlebotomy-induced stress erythropoiesis (abruptly dropping hemoglobin to 3-4 g/dl over 4-5 hr) and the pharmacodynamic (PD) relationship to the stimulated erythropoietin (EPO) ...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-005-0009-3
更新日期:2005-08-01 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::The study aimed to characterize the population pharmacokinetics of amodiaquine (AQ) and its major metabolite N-desethylamodiaquine (N-DEAQ), and to assess the correlation between exposure to N-DEAQ and treatment outcome. Blood samples from children in two studies in Zanzibar and one in Papua New Guinea were included i...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-007-9064-2
更新日期:2007-10-01 00:00:00
abstract::A hazard model of fracture was developed using individual patient data (IPD) from the NHANES (2005-2008) database and summary-level data from an aggregate dataset (AD). The AD was built by performing a comprehensive and systematic literature search of clinical studies published from 1995 to 2015, recording fracture ra...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-017-9551-z
更新日期:2017-12-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a chronic obstructive disease of the airways. An exacerbation of COPD is defined as shortness of breath, cough, and sputum production. New therapies for COPD exacerbations are examined in clinical trials frequently based on the number of exacerbations that implies long-t...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-019-09643-6
更新日期:2019-08-01 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::There has been little evaluation of maximum likelihood approximation methods for non-linear mixed effects modelling of count data. The aim of this study was to explore the estimation accuracy of population parameters from six count models, using two different methods and programs. Simulations of 100 data sets were per...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-009-9126-8
更新日期:2009-08-01 00:00:00
abstract::A method based on the multivariate technique known as principal component analysis is proposed to obtain starting values for the rate constants of indirect response models. The method is not iterative and only requires standard deviation calculations for two quantities, which are simple functions of the measured pharm...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1023/b:jopa.0000029487.21238.5c
更新日期:2004-02-01 00:00:00
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 Statu...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-015-9408-2
更新日期:2015-04-01 00:00:00
abstract::Previously, we developed a feedback model to describe the tolerance and oscillatory rebound of non-esterified fatty acid (NEFA) plasma concentrations in male Sprague Dawley rats after intravenous infusions of nicotinic acid (NiAc). This study challenges that model, using the following regimens of intravenous and oral ...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-013-9325-1
更新日期:2013-08-01 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::Multiple classes of antihypertensive drugs inhibit components of the renin-angiotensin-aldosterone system (RAAS). The primary physiological effector of the RAAS is angiotensin II (AngII) bound to the AT1 receptor (AT1-bound AngII). There is a strong non-linear feedback from AT1-bound AngII on renin secretion. Since AT...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-018-9612-y
更新日期:2019-02-01 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::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::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::Structural identifiability is an often overlooked, but essential, prerequisite to the experiment design stage. The application of structural identifiability analysis to models of myelosuppression is used to demonstrate the importance of its considerations. It is shown that, under certain assumptions, these models are ...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章,meta分析
doi:10.1007/s10928-018-9569-x
更新日期:2018-02-01 00:00:00
abstract::Mixture modeling within the context of pharmacokinetic (PK)/pharmacodynamic (PD) mixed effects modeling is a useful tool to explore a population for the presence of two or more subpopulations, not explained by evaluated covariates. At present, statistical tests for the existence of mixed populations have not been deve...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1023/a:1025564409649
更新日期:2003-06-01 00:00:00
abstract::The volume of distribution at steady state (Vss) of therapeutic proteins is usually assessed by non-compartmental or compartmental pharmacokinetic (PK) analysis wherein errors may arise due to the elimination of therapeutic proteins from peripheral tissues that are not in rapid equilibrium with the sampling compartmen...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-011-9209-1
更新日期:2011-10-01 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::Stepwise covariate modeling (SCM) is a widely used tool in pharmacometric analyses to identify covariates that explain between-subject variability (BSV) in exposure and exposure-response relationships. However, this approach has several potential weaknesses, including over-estimated covariate effect and incorrect sele...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-019-09635-6
更新日期:2019-06-01 00:00:00
abstract::Several reviews on specific topics related to positron emission tomography (PET) ranging in complexity from introductory to highly technical have already been published. This introduction to the analysis of PET data was written as a simple guide of the different phases of analysis of a given PET dataset, from acquisit...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章,评审
doi:10.1007/s10928-013-9307-3
更新日期:2013-08-01 00:00:00