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A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence

To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sod...

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Autores principales: Uno, Yuko, Ogawa, Emiyu, Aiyoshi, Eitaro, Arai, Tsunenori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466385/
https://www.ncbi.nlm.nih.gov/pubmed/30583456
http://dx.doi.org/10.3390/bioengineering6010001
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author Uno, Yuko
Ogawa, Emiyu
Aiyoshi, Eitaro
Arai, Tsunenori
author_facet Uno, Yuko
Ogawa, Emiyu
Aiyoshi, Eitaro
Arai, Tsunenori
author_sort Uno, Yuko
collection PubMed
description To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sodium plasma concentration and myocardial fluorescence. Differential rate equations of talaporfin sodium concentration in the plasma, interstitial space, and cell compartment were developed with individual compartment volume, concentration, and rate constants. Using measured volume ratios based on histological examinations, we defined that the myocardial fluorescence consisted of the linear addition of fluorescence generated from these three compartments. The rate constants were obtained by fitting to minimize the sum of the squared errors between the measured talaporfin sodium concentrations and the calculated concentrations divided by the number of data points using the conjugate gradient method in MATLAB. We confirmed that this fitting operation may be appropriate, because a coefficient of determination between the measured talaporfin sodium changes and the calculated concentrations using our equations was 0.99. Consequently, to estimate the interstitial concentration in the canine myocardium, we propose a three-compartment pharmacokinetic model construction methodology using measured changes in talaporfin sodium plasma concentration and changes in myocardial fluorescence.
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spelling pubmed-64663852019-04-19 A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence Uno, Yuko Ogawa, Emiyu Aiyoshi, Eitaro Arai, Tsunenori Bioengineering (Basel) Article To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sodium plasma concentration and myocardial fluorescence. Differential rate equations of talaporfin sodium concentration in the plasma, interstitial space, and cell compartment were developed with individual compartment volume, concentration, and rate constants. Using measured volume ratios based on histological examinations, we defined that the myocardial fluorescence consisted of the linear addition of fluorescence generated from these three compartments. The rate constants were obtained by fitting to minimize the sum of the squared errors between the measured talaporfin sodium concentrations and the calculated concentrations divided by the number of data points using the conjugate gradient method in MATLAB. We confirmed that this fitting operation may be appropriate, because a coefficient of determination between the measured talaporfin sodium changes and the calculated concentrations using our equations was 0.99. Consequently, to estimate the interstitial concentration in the canine myocardium, we propose a three-compartment pharmacokinetic model construction methodology using measured changes in talaporfin sodium plasma concentration and changes in myocardial fluorescence. MDPI 2018-12-21 /pmc/articles/PMC6466385/ /pubmed/30583456 http://dx.doi.org/10.3390/bioengineering6010001 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Uno, Yuko
Ogawa, Emiyu
Aiyoshi, Eitaro
Arai, Tsunenori
A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
title A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
title_full A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
title_fullStr A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
title_full_unstemmed A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
title_short A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence
title_sort three-compartment pharmacokinetic model to predict the interstitial concentration of talaporfin sodium in the myocardium for photodynamic therapy: a method combining measured fluorescence and analysis of the compartmental origin of the fluorescence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466385/
https://www.ncbi.nlm.nih.gov/pubmed/30583456
http://dx.doi.org/10.3390/bioengineering6010001
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