A Dermal Absorption Model Validated By Linkage to a PBPK Model For Chloroform

Epidemiology ◽  
2006 ◽  
Vol 17 (Suppl) ◽  
pp. S246
Author(s):  
H Shi ◽  
A C. Ferguson ◽  
P Beamer ◽  
J O. Leckie
Keyword(s):  
Pbpk Model ◽  
Dermal Absorption ◽  
Absorption Model

Development of a Cumulative Dermal Absorption Model by Linkage to a PBPK Model for Chlorpyrifos and Diazinon

Epidemiology ◽  
2006 ◽  
Vol 17 (Suppl) ◽  
pp. S246-S247
Author(s):  
P Beamer ◽  
H Shi ◽  
A Ferguson ◽  
J Leckie
Keyword(s):  
Pbpk Model ◽  
Dermal Absorption ◽  
Absorption Model

scholarly journals Development and Evaluation of an In Silico Dermal Absorption Model Relevant for Children

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 172
Author(s):  
Yejin Esther Yun ◽  
Daniella Calderon-Nieva ◽  
Abdullah Hamadeh ◽  
Andrea N. Edginton
Keyword(s):  
Skin Permeation ◽  
Human Health Risk ◽  
Weight Ratio ◽  
Predictive Performance ◽  
Chemical Exposure ◽  
Dermal Absorption ◽  
Model Parameters ◽  
Absorption Model ◽  
Comprehensive Review ◽  
Age Dependent

The higher skin surface area to body weight ratio in children and the prematurity of skin in neonates may lead to higher chemical exposure as compared to adults. The objectives of this study were: (i) to provide a comprehensive review of the age-dependent anatomical and physiological changes in pediatric skin, and (ii) to construct and evaluate an age-dependent pediatric dermal absorption model. A comprehensive review was conducted to gather data quantifying the differences in the anatomy and physiology of child and adult skin. Maturation functions were developed for model parameters that were found to be age-dependent. A pediatric dermal absorption model was constructed by updating a MoBi implementation of the Dancik et al. 2013 skin permeation model with these maturation functions. Using a workflow for adult-to-child model extrapolation, the predictive performance of the model was evaluated by comparing its predicted rates of flux of diamorphine, phenobarbital and buprenorphine against experimental observations using neonatal skin. For diamorphine and phenobarbital, the model provided reasonable predictions. The ratios of predicted:observed flux in neonates for diamorphine ranged from 0.55 to 1.40. For phenobarbital, the ratios ranged from 0.93 to 1.26. For buprenorphine, the model showed acceptable predictive performance. Overall, the physiologically based pediatric dermal absorption model demonstrated satisfactory prediction accuracy. The prediction of dermal absorption in neonates using a model-based approach will be useful for both drug development and human health risk assessment.

Soil and Vegetation Pollution from an Abandoned Mining Area Situated in Hunedoara County, Romania

2018 ◽  
Vol 69 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Cristina Dinu ◽  
Eleonora Mihaela Ungureanu ◽  
Gabriela Geanina Vasile ◽  
Lidia Kim ◽  
Ioana Ionescu ◽  
...  
Keyword(s):  
Mine Waste ◽  
High Mobility ◽  
Mining Area ◽  
Soil Samples ◽  
Dermal Absorption ◽  
Abandoned Mines ◽  
Emission Spectrometry ◽  
Metallic Elements ◽  
Vegetation Samples ◽  
Nickel Lead

The soils situated near the abandoned mines are highly polluted with metals due to the discharge and dispersion of mine waste into nearby air, water (surface and groundwater) and soil. Heavy metals may be transferred to humans through ingestion, inhalation or dermal absorption and can produce serious health problems affect the nervous, endocrine and immune systems, hematopoietic function and cellular metabolism. This paper investigates the presence of metallic elements from fourteen soil samples (seven sampling points) and thirty-six vegetation samples (different types of leaves, plants, roots and tree barks). The samples were collected from six different sites located in an abandoned mining area and from a point (blank sample) located 5 km in the SV direction of the quarry. The results obtained for soil samples show an overrun of the alert and / or intervention threshold for the following metals: arsenic, cadmium, cobalt, copper, manganese, nickel, lead and zinc. The analytical investigation for vegetation samples indicated that concentration for calcium, magnesium, cadmium, chromium, manganese, nickel, lead, zinc were situated over the normal range in some samples. The analytical investigations were performed by optical emission spectrometry (ICP-OES). The study�s conclusion indicates that, as result of soil acidic pH and high mobility of some metals, metallic elements migrate from soil to vegetation.

scholarly journals Development of Physiologically Based Pharmacokinetic Model for Orally Administered Fexuprazan in Humans

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 813
Author(s):  
Yoo-Seong Jeong ◽  
Min-Soo Kim ◽  
Nora Lee ◽  
Areum Lee ◽  
Yoon-Jee Chae ◽  
...  
Keyword(s):  
Gastric Acid ◽  
Pbpk Model ◽  
Pbpk Modeling ◽  
Drug Candidate ◽  
Metabolite Formation ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

Fexuprazan is a new drug candidate in the potassium-competitive acid blocker (P-CAB) family. As proton pump inhibitors (PPIs), P-CABs inhibit gastric acid secretion and can be used to treat gastric acid-related disorders such as gastroesophageal reflux disease (GERD). Physiologically based pharmacokinetic (PBPK) models predict drug interactions as pharmacokinetic profiles in biological matrices can be mechanistically simulated. Here, we propose an optimized and validated PBPK model for fexuprazan by integrating in vitro, in vivo, and in silico data. The extent of fexuprazan tissue distribution in humans was predicted using tissue-to-plasma partition coefficients in rats and the allometric relationships of fexuprazan distribution volumes (VSS) among preclinical species. Urinary fexuprazan excretion was minimal (0.29–2.02%), and this drug was eliminated primarily by the liver and metabolite formation. The fraction absorbed (Fa) of 0.761, estimated from the PBPK modeling, was consistent with the physicochemical properties of fexuprazan, including its in vitro solubility and permeability. The predicted oral bioavailability of fexuprazan (38.4–38.6%) was within the range of the preclinical datasets. The Cmax, AUClast, and time-concentration profiles predicted by the PBPK model established by the learning set were accurately predicted for the validation sets.

scholarly journals Indirect light absorption model for highly strained silicon infrared sensors

2021 ◽  
Vol 130 (5) ◽  
pp. 055105
Author(s):  
Nicolas Roisin ◽  
Guillaume Brunin ◽  
Gian-Marco Rignanese ◽  
Denis Flandre ◽  
Jean-Pierre Raskin
Keyword(s):  
Light Absorption ◽  
Strained Silicon ◽  
Absorption Model ◽  
Infrared Sensors ◽  
Highly Strained

scholarly journals Mechanistic physiology-based pharmacokinetic modeling to elucidate vincristine-induced peripheral neuropathy following treatment with novel kinase inhibitors

2021 ◽  
Author(s):  
Venkatesh Pilla Reddy ◽  
Adrian J. Fretland ◽  
Diansong Zhou ◽  
Shringi Sharma ◽  
Buyun Chen ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Kinase Inhibitors ◽  
Pbpk Model ◽  
Model Development ◽  
Limited Information ◽  
Time Curve ◽  
Btk Inhibitor ◽  
Chop Therapy

Abstract Purpose Limited information is available regarding the drug–drug interaction (DDI) potential of molecular targeted agents and rituximab plus cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), and prednisone (R-CHOP) therapy. The addition of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib to R-CHOP therapy results in increased toxicity versus R-CHOP alone, including higher incidence of peripheral neuropathy. Vincristine is a substrate of P-glycoprotein (P-gp, ABCB1); drugs that inhibit P-gp could potentially cause increased toxicity when co-administered with vincristine through DDI. While the combination of the BTK inhibitor acalabrutinib and R-CHOP is being explored clinically, the DDI potential between these therapies is unknown. Methods A human mechanistic physiology-based pharmacokinetic (PBPK) model of vincristine following intravenous dosing was developed to predict potential DDI interactions with combination therapy. In vitro absorption, distribution, metabolism, and excretion and in vivo clinical PK parameters informed PBPK model development, which was verified by comparing simulated vincristine concentrations with observed clinical data. Results While simulations suggested no DDI between vincristine and ibrutinib or acalabrutinib in plasma, simulated vincristine exposure in muscle tissue was increased in the presence of ibrutinib but not acalabrutinib. Extrapolation of the vincristine mechanistic PBPK model to other P-gp substrates further suggested DDI risk when ibrutinib (area under the concentration–time curve [AUC] ratio: 1.8), but not acalabrutinib (AUC ratio: 0.92), was given orally with venetoclax or digoxin. Conclusion Overall, these data suggest low DDI risk between acalabrutinib and P-gp substrates with negligible increase in the potential risk of vincristine-induced peripheral neuropathy when acalabrutinib is added to R-CHOP therapy.

scholarly journals Comprehensive PBPK Model to Predict Drug Interaction Potential of Zanubrutinib as a Victim or Perpetrator

2021 ◽  
Author(s):  
Kun Wang ◽  
Xueting Yao ◽  
Miao Zhang ◽  
Dongyang Liu ◽  
Yuying Gao ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Interaction Potential ◽  
Pbpk Model
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