Construction of a Physiologically Based Pharmacokinetic Model for 2,4-Dichlorophenoxyacetic Acid Dosimetry in the Developing Rabbit Brain

Kim, C.S.; Binienda, Zbigniew; Sandberg, Jennifer A.

doi:10.1006/taap.1996.0032

Cited by 28 publications

(14 citation statements)

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“…However, if a chemical has been conjugated by the fetus (e.g., glucuronidation, sulfation) or otherwise metabolized to a more polar form, the rate of return to the maternal circulation will be slower than that for the parent compound (Dancis et al 1958;Goebelsmann et al 1968Goebelsmann et al , 1972Levitz et al 1960). PBPK models to predict the fate of toxicants in fetal tissues as a function of development are emerging (Kim et al 1996;Sandberg et al 1996).…”

Section: Phase Ii: Data Analysis and Development Of Risk Assessment Amentioning

confidence: 99%

Incorporating children's toxicokinetics into a risk framework.

Ginsberg

Slikker

Bruckner

et al. 2004

Environ Health Perspect

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Children's responses to environmental toxicants will be affected by the way in which their systems absorb, distribute, metabolize, and excrete chemicals. These toxicokinetic factors vary during development, from in utero where maternal and placental processes play a large role, to the neonate in which emerging metabolism and clearance pathways are key determinants. Toxicokinetic differences between neonates and adults lead to the potential for internal dosimetry differences and increased or decreased risk, depending on the mechanisms for toxicity and clearance of a given chemical. This article raises a number of questions that need to be addressed when conducting a toxicokinetic analysis of in utero or childhood exposures. These questions are organized into a proposed framework for conducting the assessment that involves problem formulation (identification of early life stage toxicokinetic factors and chemical-specific factors that may raise questions/concerns for children); data analysis (development of analytic approach, construction of child/adult or child/animal dosimetry comparisons); and risk characterization (evaluation of how children's toxicokinetic analysis can be used to decrease uncertainties in the risk assessment). The proposed approach provides a range of analytical options, from qualitative to quantitative, for assessing children's dosimetry. Further, it provides background information on a variety of toxicokinetic factors that can vary as a function of developmental stage. For example, the ontology of metabolizing systems is described via reference to pediatric studies involving therapeutic drugs and evidence from in vitro enzyme studies. This type of resource information is intended to help the assessor begin to address the issues raised in this paper.

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Section: Phase Ii: Data Analysis and Development Of Risk Assessment Amentioning

confidence: 99%

Incorporating children's toxicokinetics into a risk framework.

Ginsberg

Slikker

Bruckner

et al. 2004

Environ Health Perspect

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“…One of these parameters, which is essential to solve the mass balance differential equations for these models, is the partition coefficients. The radiolabeled LPS was used for the measurement of tissue partitioning with the technique of in vitro tissue slice incubation as previously described (Kim et al, 1996). The tissue : plasma or tissue : CSF partition coefficients are endotoxin-specific input parameters in the PBPK model.…”

Section: Discussionmentioning

confidence: 99%

Determination of the rat tissue partitioning of endotoxin in vitro for physiologically‐based pharmacokinetic (PBPK) modeling

Ross

Sapienza

Hanes

et al. 2004

J of Applied Toxicology

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The biosynthetically double-labeled lipopolysaccharide (LPS), containing (3)H-labeled on the fatty acyl-chains and (14)C-labeled on the glucosamine of Salmonella enterica serotype typhimurium, was isolated from bacteria grown in proteose peptone-beef extract (PPBE) medium in the presence of labeled precursors; 133 micro Ci/ml of [2-(3)H] acetate sodium salt and 0.167 micro Ci/ml of N-acetyl[D-1-(14)C]glucosamine. The LPS was extracted from the bacteria with 90% phenol/chloroform/petroleum ether, purified and stored in 0.1% (v/v) triethylamine/10 mM Tris HCl at -70 degrees C. Tissue slices and portions of the meninges were prepared and incubated in artificial cerebrospinal fluid (CSF) or Krebs phosphate buffer (Krebs) containing 150 ng/ml LPS with [(3)H] LPS (0.004 micro Ci/ml, sp. act. 28 micro Ci/mg LPS). The tissues were incubated under 95% oxygen/5% carbon dioxide at 37 degrees C with constant agitation until steady-state uptake was reached (60 min). At the end of the incubation period, tissues were processed for radioactivity measurement. The rat tissue partitioning of LPS in artificial CSF for brain and Krebs for other organs was measured by using the ratio of tissue to medium at the steady state in vitro. The following results were obtained from the study: Heart, 0.15; liver, 0.19; spleen, 0.12; kidney, 0.18; stomach, 0.17; small intestine, 0.18; brain stem, 0.10; cerebellum, 0.11; meninges, 0.77; hippocampus, 0.12; hypothalamus, 0.12; frontal cortex, 0.09 and caudate nucleus, 0.10. This information, along with plasma or blood/buffer partition coefficients, is a requisite for constructing a physiologically-based pharmacokinetic (PBPK) model of endotoxins for quantitative risk assessment.

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“…During the following years, these models were used as a basis for further refinement in the field of human health risk assessment . At the same time, other models were also developed de novo . PBPK models for pregnant animals were soon extrapolated to human pregnancy and used to estimate the reference dose and concentration of different chemicals, such as methylmercury, ethylene glycol monomethyl ether, and acetone .…”

Section: History and Recent Progress Of Pregnancy Pbpk Modelsmentioning

confidence: 99%

“…PBPK models were considered minimal if the model was semimechanistic in that it included no more than seven compartments (including the blood, gastrointestinal tract, liver, a fetoplacental unit, and up to three additional compartments). Many pregnancy PBPK models were developed using acslX as the simulation language, but other tools have also been employed, such as the SimuSolv software by Kim et al . or MatLab (MathWorks, Natick, MA) by El‐Masri et al .…”

Section: History and Recent Progress Of Pregnancy Pbpk Modelsmentioning

confidence: 99%

Physiologically Based Pharmacokinetic Modeling in Pregnancy: A Systematic Review of Published Models

Dallmann

Pfister

Anker

et al. 2018

Clin Pharma and Therapeutics

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During recent years there has been a surge in developing and applying physiologically based pharmacokinetic (PBPK) models in pregnant women to better understand and predict changes in drug pharmacokinetics throughout pregnancy. As a consequence, the number of publications focusing on pregnancy PBPK models has increased substantially. However, to date these models, especially across various platforms, have not been systematically evaluated. Hence, this review aims to assess published PBPK models in pregnancy used for therapeutic purposes.

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Construction of a Physiologically Based Pharmacokinetic Model for 2,4-Dichlorophenoxyacetic Acid Dosimetry in the Developing Rabbit Brain

Cited by 28 publications

References 0 publications

Incorporating children's toxicokinetics into a risk framework.

Incorporating children's toxicokinetics into a risk framework.

Determination of the rat tissue partitioning of endotoxin in vitro for physiologically‐based pharmacokinetic (PBPK) modeling

Physiologically Based Pharmacokinetic Modeling in Pregnancy: A Systematic Review of Published Models

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