Format

Send to

Choose Destination
Bioengineering (Basel). 2018 Dec 21;6(1). pii: E1. doi: 10.3390/bioengineering6010001.

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.

Author information

1
School of Fundamental Science and Technology, Graduate School of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama City, Kanagawa 223-8522, Japan. y.uno@arai.appi.keio.ac.jp.
2
School of Allied Health Science, Kitasato University, Kanagawa 252-0373, Japan. e.ogawa@kitasato-u.ac.jp.
3
The Institute of Statistical Mathematics, Tokyo 190-0014, Japan. aiyoshi0823@gmail.com.
4
School of Fundamental Science and Technology, Graduate School of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama City, Kanagawa 223-8522, Japan. tsunearai@appi.keio.ac.jp.
5
Department of Applied Physics and Physico-Informatics, Faculty of Science and Technology, Keio University, Kanagawa 223-8522, Japan. tsunearai@appi.keio.ac.jp.

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

Conflict of interest statement

A conversion constant (Rmyo) was determined using the myocardial measured fluorescence data (Mmyo) and C’myo. We assumed that the initial value of the calculated myocardial concentration [Cmyo(0)], which was obtained from Equation (6) using the determined C1(0): 59.01 μg/mL and C2(0), and C3(0): 0 μg/mL described in Section 2.4, was equal to the initial value of the myocardial measured concentration data [C’myo(0)]. Rmyo was set to be 189 μg/(mL・counts) using Mmyo(0) = 0.025 counts and Cmyo(0) = 4.72 μg/mL.

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center