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.
Highlights
We have studied the application of an extracellular photosensitization reaction (PR) using talaporfin sodium to realize a low-temperature-elevation myocardial arrhythmia ablation method [1,2,3,4]
We developed a three-compartment pharmacokinetic model to estimate the interstitial concentration of talaporfin sodium in canines using measured talaporfin sodium myocardial fluorescence
To estimate canine myocardial interstitial concentration, we present the construction of a three-compartment pharmacokinetic model using measured talaporfin sodium plasma concentration changes and myocardial fluorescence changes with consideration of the origin of the fluorescence from the compartments with measured volume ratios based on histological examinations
Summary
We have studied the application of an extracellular photosensitization reaction (PR) using talaporfin sodium to realize a low-temperature-elevation myocardial arrhythmia ablation method [1,2,3,4].We developed a three-compartment pharmacokinetic model to estimate the interstitial concentration of talaporfin sodium in canines using measured talaporfin sodium myocardial fluorescence. Bioengineering 2019, 6, 1 in Japan, is a second-generation photosensitizer and has an absorbance peak at 664 nm in the Q band [5] This method is based on a PR with a high concentration of talaporfin sodium in the myocardial interstitial space, because of a short drug-light interval [1,2,3,4]. With singlet oxygen production outside myocardial cell, an immediate electrical conduction block can be realized within a few minutes in animal models [6]. In this scheme, the myocardial interstitial space is our targeted PR region, and concentration changes of talaporfin sodium in the interstitial space are needed to obtain the maximal interaction efficacy. The constructed three-compartment pharmacokinetic model can provide very useful information
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