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 included in this study were the offspring of diabetic parents and were followed up to 25 years. Repeated fasting blood samples were collected during the follow-up. Longitudinal data of four DDVs, namely fasting blood glucose (FBG), fasting serum insulin (FSI), homeostatic model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) were recorded and compared. According to the diabetes status at the end of the follow-up, the data analysis involved a progressor group of 25 subjects, and a non-progressor group of 127 subjects. The temporal changes in the four DDVs over the time course of the disease development were evaluated by a single-slope and a dual-slope population-based Bayesian model. A dual-slope model based on FBG was found to be the best disease development model. For non-progressors, the FBG baseline stayed at 69.2 [66.5, 72.1] mg/dl (Bayes estimate [95% Bayesian credible set]) and increased with age by a rate of 0.227 mg/dl [0.149, 0.3] per year. For the progressors, the FBG increase with age the same rate as non-progressors and started to have an additional increase of 2.27 [0.505, 4.52] mg/dl per year, starting 8.73 [-10.8, -6.93] years before the diagnosis of T2D. No significant longitudinal increasing or decreasing temporal pattern was found for FSI, HOMA-IR and BMI by the population-based Bayesian approach. The proposed model, which enables a quantitative, time-based evaluation of the development of T2D in this higher risk population, may be used to quantify the effect of interventions/prevention strategies such as drug treatment and lifestyle changes.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Lin CW,Warram JH,Veng-Pedersen Pdoi
10.1007/s10928-011-9208-2subject
Has Abstractpub_date
2011-10-01 00:00:00pages
563-79issue
5eissn
1567-567Xissn
1573-8744journal_volume
38pub_type
杂志文章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::HbA1c is the most commonly used biomarker for the adequacy of glycemic management in diabetic patients and a surrogate endpoint for anti-diabetic drug approval. In spite of an empirical description for the relationship between average glucose (AG) and HbA1c concentrations, obtained from the A1c-derived average glucose...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-012-9289-6
更新日期:2013-04-01 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::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::The number of counts (events) per unit of time is a discrete response variable that is generally analyzed with the Poisson distribution (PS) model. The PS model makes two assumptions: the mean number of counts (lambda) is assumed equal to the variance, and counts occurring in non-overlapping intervals are assumed inde...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10928-009-9131-y
更新日期:2009-10-01 00:00:00
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
更新日期:2018-10-01 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::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::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::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::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::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::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
更新日期:2016-02-01 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::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::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::Although selective 5-HT reuptake inhibitors (SSRIs) block monoamine uptake within hours of administration to patients, their full clinical effect does not appear until 2-4 weeks after treatment onset. Pindolol, a betablocker with weak partial 5-HT1A receptor agonist activity has been shown to produce a more rapid onse...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-005-0006-6
更新日期:2005-12-01 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::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::In the present pharmacokinetic/pharmacodynamic (PK/PD) evaluation, cortisol, total lymphocytes, and lymphocyte subpopulations were monitored following single oral doses of two oral formulations of 3 mg budesonide (BUD) (Dosage Forms A and B) in order to assess the differential effects that BUD may have on cortisol sup...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-006-9013-5
更新日期:2006-08-01 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::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::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::A modeling and simulation approach was used for quantitative comparison of a new generation HER2 antibody drug conjugate (ADC, PF-06804103) with trastuzumab-DM1 (T-DM1). To compare preclinical efficacy, the pharmacokinetic (PK)/pharmacodynamic (PD) relationship of PF-06804103 and T-DM1 was determined across a range of...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-020-09702-3
更新日期:2020-10-01 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::In this work a model for analyzing categorical data is presented; the differential odds model. Unlike the commonly used proportional odds model, this model does not assume that a covariate affects all categories equally on the log odds scale. The differential odds model was compared to the proportional odds model, by ...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-008-9098-0
更新日期:2008-10-01 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::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::Literature data are often reported as multiple (longitudinal) mean outcomes observed in several groups of patients within a study. Observations within a study are correlated because the patients come from a common population, and the mean observations over time within a treatment arm are correlated because they are ba...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-010-9152-6
更新日期:2010-04-01 00:00:00
abstract::The population approach to estimating mixed effects model parameters of interest in pharmacokinetic (PK) studies has been demonstrated to be an effective method in quantifying relevant population drug properties. The information available for each individual is usually sparse. As such, care should be taken to ensure t...
journal_title:Journal of pharmacokinetics and pharmacodynamics
pub_type: 杂志文章
doi:10.1007/s10928-005-2102-z
更新日期:2005-02-01 00:00:00