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 micrograms i.v. and s.c.) with an intervening washout period of 7 days. Serum concentrations of Filgrastim were determined using an enzyme-linked immunosorbent assay. Absolute neutrophil count (ANC) was determined. Data analysis was performed using mixed-effects modeling as implemented in the NONMEM software package. The final PKPD model incorporates a two-compartment PK model with bisegmental absorption from the s.c. site, first-order and saturable elimination pathways, and an indirect PD model. A sigmoidal Emax model for the stimulation of ANC input rate (kin) was superior to the conventional Emax model (mean +/- SE: Emax = 12.7 +/- 1.7; EC50 = 4.72 +/- 0.72 ng/ml; Hill = 1.34 +/- 0.19). In addition, a time-variant scaling factor for ANC observations was introduced to account for the early transient depression of ANC after Filgrastim administration. The absolute bioavailability of subcutaneously administered Filgrastim was estimated to be 0.619 +/- 0.058 and 0.717 +/- 0.028 for 375 micrograms and 750 micrograms s.c. doses, respectively. The time profiles of concentration and ANC, as well as the concentration approximately ANC relationship of Filgrastim in healthy volunteers were well described by the developed population PK-PD model.
journal_name
J Pharmacokinet Pharmacodynjournal_title
Journal of pharmacokinetics and pharmacodynamicsauthors
Wang B,Ludden TM,Cheung EN,Schwab GG,Roskos LKdoi
10.1023/a:1011534529622keywords:
subject
Has Abstractpub_date
2001-08-01 00:00:00pages
321-42issue
4eissn
1567-567Xissn
1573-8744journal_volume
28pub_type
杂志文章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：: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
更新日期：2014-08-01 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：: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：: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：: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：: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
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：: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
更新日期：2011-10-01 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：: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：: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：: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：: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：: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：: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：: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
更新日期：2014-06-01 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 distributed delay model has been introduced that replaces the transit compartments in the classic model of chemotherapy-induced myelosuppression with a convolution integral. The maturation of granulocyte precursors in the bone marrow is described by the gamma probability density function with the shape parameter (...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章
doi：10.1007/s10928-018-9575-z
更新日期：2018-04-01 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：: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
更新日期：2002-08-01 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：: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：: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：:We develop a mechanistic model for post-operative pain and apply it to describe the pharmacodynamic effects of the kappa-opioids nalbuphine and naloxone administered either alone or in combination in patients after surgical removal of one or more madibular third molar teeth. Data were obtained from 6 clinical studies ...
journal_title：Journal of pharmacokinetics and pharmacodynamics
pub_type： 杂志文章,随机对照试验
doi：10.1007/s10928-007-9076-y
更新日期：2008-02-01 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 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：: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：: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：: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
