Abstract：
:To shed light on how acute exercise affects blood glucose (BG) concentrations in nondiabetic subjects, we develop a physiological pharmacokinetic/pharmacodynamic model of postprandial glucose dynamics during exercise. We unify several concepts of exercise physiology to derive a multiscale model that includes three important effects of exercise on glucose dynamics: increased endogenous glucose production (EGP), increased glucose uptake in skeletal muscle (SM), and increased glucose delivery to SM by capillary recruitment (i.e. an increase in surface area and blood flow in capillary beds). We compare simulations to experimental observations taken in two cohorts of healthy nondiabetic subjects (resting subjects (n = 12) and exercising subjects (n = 12)) who were each given a mixed-meal tolerance test. Metabolic tracers were used to quantify the glucose flux. Simulations reasonably agree with postprandial measurements of BG concentration and EGP during exercise. Exercise-induced capillary recruitment is predicted to increase glucose transport to SM by 100%, causing hypoglycemia. When recruitment is blunted, as in those with capillary dysfunction, the opposite occurs and higher than expected BG levels are predicted. Model simulations show how three important exercise-induced phenomena interact, impacting BG concentrations. This model describes nondiabetic subjects, but it is a first step to a model that describes glucose dynamics during exercise in those with type 1 diabetes (T1D). Clinicians and engineers can use the insights gained from the model simulations to better understand the connection between exercise and glucose dynamics and ultimately help patients with T1D make more informed insulin dosing decisions around exercise.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Frank S,Jbaily A,Hinshaw L,Basu R,Basu A,Szeri AJdoi
10.1007/s10928-020-09726-9subject
Has Abstractpub_date
2021-01-04 00:00:00eissn
1567-567Xissn
1573-8744pii
10.1007/s10928-020-09726-9pub_type
杂志文章abstract：:Cancer therapies that harness the actions of the immune response, such as targeted monoclonal antibody treatments and therapeutic vaccines, are relatively new and promising in the landscape of cancer treatment options. Mathematical modeling and simulation of immune-modifying therapies can help to offset the costs of d...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-014-9386-9
更新日期：2014-10-01 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：: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
更新日期：2018-02-01 00:00:00
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
更新日期：2009-02-01 00:00:00
abstract：:Altered expressions of the key enzymes in arachidonic acid (AA) metabolism, prostaglandin synthase 1 and 2 and cysteinyl leukotriene C(4) synthase, are of importance in understanding aspirin-induced asthma. We propose a mathematical model of AA metabolism and its interaction with non-steroidal anti-inflammatory drugs ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-011-9192-6
更新日期：2011-04-01 00:00:00
abstract：:A population pharmacokinetic analysis was conducted to characterize the pharmacokinetics of fexofenadine in Japanese pediatric patients (6 months through 16 years) with perennial allergic rhinitis or atopic dermatitis. The dataset was composed of 515 patients (including 109 adults), for a total of 1,080 concentration-...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 临床试验,杂志文章
doi：10.1007/s10928-014-9356-2
更新日期：2014-04-01 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
abstract：:This study was designed to investigate ethnic differences in the pharmacokinetics (PKs) of moxifloxacin and its metabolites, M1 (sulfo conjugate) and M2 (acyl-glucuronate), among Japanese, Chinese, and Korean populations, following oral administration. We used a population PK modeling approach using data from a clinic...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-017-9556-7
更新日期：2018-04-01 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：: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
abstract：:We explore the use of fractional order differential equations for the analysis of datasets of various drug processes that present anomalous kinetics, i.e. kinetics that are non-exponential and are typically described by power-laws. A fractional differential equation corresponds to a differential equation with a deriva...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-009-9116-x
更新日期：2009-04-01 00:00:00
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：: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：: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：:We investigated the propagation of population pharmacokinetic information across clinical studies by applying Bayesian techniques. The aim was to summarize the population pharmacokinetic estimates of a study in appropriate statistical distributions in order to use them as Bayesian priors in consequent population pharm...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-005-0048-9
更新日期：2005-08-01 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：: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：: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：: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：: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：: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：:Bioequivalence testing has been traditionally centered in summary variables such as AUC, C (max) and t (max) which filter out the intrinsic information conveyed by discrete sequential concentration-time observations. Comparing entire concentration-time profiles between test and reference formulations for bioequivalenc...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-007-9055-3
更新日期：2007-08-01 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：: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：:Drugs that bind with high affinity and to a significant extent (relative to dose) to a pharmacologic target such as an enzyme, receptor, or transporter may exhibit nonlinear pharmacokinetic (PK) behavior. Processes such as receptor-mediated endocytosis may result in drug elimination. A general PK model for characteriz...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1023/a:1014414520282
更新日期：2001-12-01 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：: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：: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：: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 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
更新日期：2001-08-01 00:00:00
