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

Yuko Uno, Emiyu Ogawa, Eitaro Aiyoshi, Tsunenori Arai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number1
JournalBioengineering
Volume6
Issue number1
DOIs
Publication statusPublished - 2019 Jan 22

Fingerprint

Photodynamic therapy
Pharmacokinetics
Fluorescence
Sodium
Plasmas
Rate constants
Conjugate gradient method
MATLAB
Talaporfin

Keywords

  • Interstitial space
  • Myocardial fluorescence
  • Pharmacokinetics
  • Talaporfin sodium
  • Three-compartment model

ASJC Scopus subject areas

  • Bioengineering

Cite this

@article{65bff7f8134e426fa88ef8e558c99ba1,
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",
abstract = "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.",
keywords = "Interstitial space, Myocardial fluorescence, Pharmacokinetics, Talaporfin sodium, Three-compartment model",
author = "Yuko Uno and Emiyu Ogawa and Eitaro Aiyoshi and Tsunenori Arai",
year = "2019",
month = "1",
day = "22",
doi = "10.3390/bioengineering6010001",
language = "English",
volume = "6",
journal = "Bioengineering",
issn = "2306-5354",
publisher = "MDPI AG",
number = "1",

}

TY - JOUR

T1 - A three-compartment pharmacokinetic model to predict the interstitial concentration of talaporfin sodium in the myocardium for photodynamic therapy

T2 - A method combining measured fluorescence and analysis of the compartmental origin of the fluorescence

AU - Uno, Yuko

AU - Ogawa, Emiyu

AU - Aiyoshi, Eitaro

AU - Arai, Tsunenori

PY - 2019/1/22

Y1 - 2019/1/22

N2 - 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.

AB - 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.

KW - Interstitial space

KW - Myocardial fluorescence

KW - Pharmacokinetics

KW - Talaporfin sodium

KW - Three-compartment model

UR - http://www.scopus.com/inward/record.url?scp=85061797970&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061797970&partnerID=8YFLogxK

U2 - 10.3390/bioengineering6010001

DO - 10.3390/bioengineering6010001

M3 - Article

AN - SCOPUS:85061797970

VL - 6

JO - Bioengineering

JF - Bioengineering

SN - 2306-5354

IS - 1

M1 - 1

ER -