当前位置： SCI文献检索 > JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS期刊下所有文献 > A semi-mechanistic model of bone mineral density and bone turnover based on a circular model of bone remodeling.

A semi-mechanistic model of bone mineral density and bone turnover based on a circular model of bone remodeling.

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 model is a closed form cyclical model with four compartments representing resorption, formation, primary mineralization, and secondary mineralization. Equations describing the time course of bone turnover biomarkers were developed using the flow rate of bone cycle units (BCU) between the compartments or the amount of BCU in each compartment. A disease progression model representing bone loss in osteoporosis, a vitamin D and calcium supplementation (placebo) model, and a drug model for antiresorptive treatments were added to the model. Initial model parameter values were derived from published bone turnover data. The BCM accurately described biomarker-time profiles in postmenopausal women receiving either placebo or bisphosphonate treatment. The slow continual increase in bone mineral density (BMD) observed after 1 year of treatment was accurately described when changes in bone turnover were combined with increases in mineralization. For this purpose, the secondary mineralization compartment was replaced by three catenary chain compartments representing increasing mineral content. The refined BCM satisfactorily predicted biomarker profiles after long-term (10-year) bisphosphonate treatment. Furthermore, the model successfully described individual bone turnover markers and BMD results following treatment with denosumab in postmenopausal women. Analyses with this model could be used to optimize dosing regimens and to predict effects of novel osteoporotic treatments.

journal_name

J Pharmacokinet Pharmacodyn

journal_title

Journal of pharmacokinetics and pharmacodynamics

authors

van Schaick E,Zheng J,Perez Ruixo JJ,Gieschke R,Jacqmin P

doi

10.1007/s10928-015-9423-3

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

315-32

issue

4

eissn

1567-567X

issn

1573-8744

journal_volume

42

pub_type

杂志文章

相关文献

JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS文献大全
  • Covariate-based dose individualization of the cytotoxic drug indisulam to reduce the risk of severe myelosuppression.

    abstract：AIM:Chemotherapy with indisulam causes myelosuppression. This study aimed to evaluate the influence of patient-related covariates on pharmacokinetics and pharmacodynamics, to identify patients at risk for severe myelosuppression and to develop a dosing algorithm for treatment optimization. METHODS:Pharmacokinetic and ...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-009-9111-2

    authors： Zandvliet AS,Schellens JH,Copalu W,Beijnen JH,Huitema AD

    更新日期：2009-02-01 00:00:00

  • A method of obtaining starting values of k(in) and k(out) for the indirect response models.

    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

    authors： Mukherjee D,Hutmacher MM

    更新日期：2004-02-01 00:00:00

  • Performance in population models for count data, part I: maximum likelihood approximations.

    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

    authors： Plan EL,Maloney A,Trocóniz IF,Karlsson MO

    更新日期：2009-08-01 00:00:00

  • Optimization of clinical dosing schedule to manage neutropenia: learnings from semi-mechanistic modeling simulation approach.

    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

    authors： Guo Y,Haddish-Berhane N,Xie H,Ouellet D

    更新日期：2020-02-01 00:00:00

  • Structural identifiability and sensitivity.

    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

    authors： Iliadis A

    更新日期：2019-04-01 00:00:00

  • Physiologically based pharmacokinetic-quantitative systems toxicology and safety (PBPK-QSTS) modeling approach applied to predict the variability of amitriptyline pharmacokinetics and cardiac safety in populations and in individuals.

    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

    authors： Tylutki Z,Mendyk A,Polak S

    更新日期：2018-10-01 00:00:00

  • Modeling nicotine arterial-venous differences to predict arterial concentrations and input based on venous measurements: application to smokeless tobacco and nicotine gum.

    abstract：:Significant arterio-venous differences in nicotine concentrations have been observed during and after cigarette smoking, nicotine nasal spray, and intravenous nicotine administration. In this paper we describe a novel mathematical method for estimating arterial blood levels from venous blood level data. The model allo...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1023/a:1020957208071

    authors： Pitsiu M,Gries JM,Benowitz N,Gourlay SG,Verotta D

    更新日期：2002-08-01 00:00:00

  • Analysis of PK/PD risk factors for development of type 2 diabetes in high risk population using Bayesian analysis of glucose-insulin kinetics.

    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

    authors： Lin CW,Veng-Pedersen P

    更新日期：2009-10-01 00:00:00

  • Review on modeling anti-antibody responses to monoclonal antibodies.

    abstract：:Monoclonal antibodies (mAbs) represent a therapeutic strategy that has been increasingly used in different diseases. mAbs are highly specific for their targets leading to induce specific effector functions. Despite their therapeutic benefits, the presence of immunogenic reactions is of growing concern. The immunogenic...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章,评审

    doi：10.1007/s10928-014-9367-z

    authors： Gómez-Mantilla JD,Trocóniz IF,Parra-Guillén Z,Garrido MJ

    更新日期：2014-10-01 00:00:00

  • Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients.

    abstract：:Intravenous acetaminophen is a commonly used analgesic following surgery. The aims of this study were to determine the population pharmacokinetic profile of intravenous acetaminophen and its metabolites in adult surgical patients and to identify patient characteristics associated with acetaminophen metabolism in the p...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-014-9358-0

    authors： Owens KH,Murphy PG,Medlicott NJ,Kennedy J,Zacharias M,Curran N,Sreebhavan S,Thompson-Fawcett M,Reith DM

    更新日期：2014-06-01 00:00:00

  • Population pharmacokinetic-pharmacodynamic modeling of filgrastim (r-metHuG-CSF) in healthy volunteers.

    abstract：:The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the granulopoietic effects of Filgrastim in healthy volunteers was characterized via a population approach. Healthy male volunteers were enrolled into a four-way crossover clinical trial. Subjects received four single doses of Filgrastim (375 and 750 microgra...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1023/a:1011534529622

    authors： Wang B,Ludden TM,Cheung EN,Schwab GG,Roskos LK

    更新日期：2001-08-01 00:00:00

  • Incorporation of stochastic variability in mechanistic population pharmacokinetic models: handling the physiological constraints using normal transformations.

    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

    authors： Tsamandouras N,Wendling T,Rostami-Hodjegan A,Galetin A,Aarons L

    更新日期：2015-08-01 00:00:00

  • A reduction in between subject variability is not mandatory for selecting a new covariate.

    abstract：:Population pharmacokinetic-pharmacodynamic analysis involves nonlinear hierarchical modelling where the mean response in a population and the variability in response from different sources are studied. It generally consists of two model hierarchies: a model for residual error and a model for heterogeneity termed betwe...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-012-9256-2

    authors： Lagishetty CV,Vajjah P,Duffull SB

    更新日期：2012-08-01 00:00:00

  • Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children.

    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

    authors： Choi BM,Lee HG,Byon HJ,Lee SH,Lee EK,Kim HS,Noh GJ

    更新日期：2015-04-01 00:00:00

  • A whole-body physiologically based pharmacokinetic (WB-PBPK) model of ciprofloxacin: a step towards predicting bacterial killing at sites of infection.

    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

    authors： Sadiq MW,Nielsen EI,Khachman D,Conil JM,Georges B,Houin G,Laffont CM,Karlsson MO,Friberg LE

    更新日期：2017-04-01 00:00:00

  • Bioequivalence for highly variable drugs: regulatory agreements, disagreements, and harmonization.

    abstract：:Regulatory authorities introduced procedures in the last decade for evaluating the bioequivalence (BE) for highly variable drugs. These approaches are similar in principle but differ in details. For example, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommend differing regulatory c...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章,评审

    doi：10.1007/s10928-019-09623-w

    authors： Endrenyi L,Tothfalusi L

    更新日期：2019-04-01 00:00:00

  • The effect of using a robust optimality criterion in model based adaptive optimization.

    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

    authors： Strömberg EA,Hooker AC

    更新日期：2017-08-01 00:00:00

  • Mixture models and subpopulation classification: a pharmacokinetic simulation study and application to metoprolol CYP2D6 phenotype.

    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

    authors： Kaila N,Straka RJ,Brundage RC

    更新日期：2007-04-01 00:00:00

  • Mathematical description of drug-target interactions: application to biologics that bind to targets with two binding sites.

    abstract：:The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equati...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-017-9546-9

    authors： Gibiansky L,Gibiansky E

    更新日期：2018-02-01 00:00:00

  • A mechanism-based disease progression model for comparison of long-term effects of pioglitazone, metformin and gliclazide on disease processes underlying Type 2 Diabetes Mellitus.

    abstract：:Effective long-term treatment of Type 2 Diabetes Mellitus (T2DM) implies modification of the disease processes that cause this progressive disorder. This paper proposes a mechanism-based approach to disease progression modeling of T2DM that aims to provide the ability to describe and quantify the effects of treatment ...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-006-9008-2

    authors： de Winter W,DeJongh J,Post T,Ploeger B,Urquhart R,Moules I,Eckland D,Danhof M

    更新日期：2006-06-01 00:00:00

  • An item response theory based integrated model of headache, nausea, photophobia, and phonophobia in migraine patients.

    abstract：:This study developed an integrated model of severity scores of migraine headache and the incidence of nausea, photophobia, and phonophobia to predict the natural time course of migraine symptoms, which are likely to occur by a common disease progression mechanism. Data were acquired from two phase 3 clinical trials co...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章,随机对照试验

    doi：10.1007/s10928-018-9602-0

    authors： Chae D,Park K

    更新日期：2018-10-01 00:00:00

  • Gaining insights into the consequences of target-mediated drug disposition of monoclonal antibodies using quasi-steady-state approximations.

    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

    authors： Grimm HP

    更新日期：2009-10-01 00:00:00

  • Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol concentrations.

    abstract：:We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including p...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-014-9369-x

    authors： van de Pas NC,Rullmann JA,Woutersen RA,van Ommen B,Rietjens IM,de Graaf AA

    更新日期：2014-08-01 00:00:00

  • A Bayesian population analysis of the development of type 2 diabetes in the offspring of diabetic parents.

    abstract：:Disease progression of type 2 diabetes (T2D) has received considerable attention, but little is known about the disease development of T2D. The purposes of this study were to identify disease development variables (DDV) for development of T2D and to compare corresponding models for disease development. All subjects in...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-011-9208-2

    authors： Lin CW,Warram JH,Veng-Pedersen P

    更新日期：2011-10-01 00:00:00

  • Population pharmacokinetics of amodiaquine and desethylamodiaquine in pediatric patients with uncomplicated falciparum malaria.

    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

    authors： Hietala SF,Bhattarai A,Msellem M,Röshammar D,Ali AS,Strömberg J,Hombhanje FW,Kaneko A,Björkman A,Ashton M

    更新日期：2007-10-01 00:00:00

  • When is a metric not a metric? Remarks on direct curve comparison in bioequivalence studies.

    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

    authors： Jawień W

    更新日期：2009-06-01 00:00:00

  • A system-approach method for the adjustment of time-varying continuous drug infusion in individual patients: a simulation study.

    abstract：:The aim of this simulation study was to present a system-approach method for adjustment of continuous drug infusions at time-varying rates, aimed at achieving and then maintaining required drug concentration-time profiles in patients. The method presented can be used for safe and cost-effective individualization of dr...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：

    authors： Durisová M,Dedík L

    更新日期：2002-12-01 00:00:00

  • A population pharmacokinetic model for R- and S-citalopram and desmethylcitalopram in Alzheimer's disease patients with agitation.

    abstract：:The citalopram for Alzheimer's disease trial evaluated citalopram for the management for agitation in Alzheimer's disease patients. Sparse data was available from this elderly patient population. A nonlinear mixed effects population pharmacokinetic modeling approach was used to describe the pharmacokinetics of R- and ...

    journal_title：Journal of pharmacokinetics and pharmacodynamics

    pub_type： 杂志文章

    doi：10.1007/s10928-015-9457-6

    authors： Akil A,Bies RR,Pollock BG,Avramopoulos D,Devanand DP,Mintzer JE,Porsteinsson AP,Schneider LS,Weintraub D,Yesavage J,Shade DM,Lyketsos CG

    更新日期：2016-02-01 00:00:00

  • Estimation of parameters for the elimination of an orally administered test substance with unknown absorption.

    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

    authors： Vogt JA,Denzer C

    更新日期：2013-04-01 00:00:00

  • Introduction to the analysis of PET data in oncology.

    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

    authors： Tomasi G,Aboagye EO

    更新日期：2013-08-01 00:00:00