Ms. Yuko Uno Profile

Yuko Uno

at Keio Univ

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Publications (2)

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Proceedings Article | 12 February 2018 Paper

3-compartment talaporfin sodium pharmacokinetic model by optimization using fluorescence measurement data from canine skin to estimate the concentration in interstitial space

Yuko Uno, Emiyu Ogawa, Eitaro Aiyoshi, Tsunenori Arai

Proceedings Volume 10476, 1047611 (2018) https://doi.org/10.1117/12.2289199

KEYWORDS: Skin, Sodium, Plasma, Luminescence, Data modeling, Optimization (mathematics), Shape memory alloys, MATLAB, Animal model studies, Tissues

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We constructed the 3-compartment talaporfin sodium pharmacokinetic model for canine by an optimization using the fluorescence measurement data from canine skin to estimate the concentration in the interstitial space. It is difficult to construct the 3-compartment model consisted of plasma, interstitial space, and cell because there is a lack of the dynamic information. Therefore, we proposed the methodology to construct the 3-compartment model using the measured talaporfin sodium skin fluorescence change considering originated tissue part by a histological observation. In a canine animal experiment, the talaporfin sodium concentration time history in plasma was measured by a spectrophotometer with a prepared calibration curve. The time history of talaporfin sodium Q-band fluorescence on left femoral skin of a beagle dog excited by talaporfin sodium Soret-band of 409 nm was measured in vivo by our previously constructed measurement system. The measured skin fluorescence was classified to its source, that is, specific ratio of plasma, interstitial space, and cell. We represented differential rate equations of the talaporfin sodium concentration in plasma, interstitial space, cell. The specific ratios and a converting constant to obtain absolute value of skin concentration were arranged. Minimizing the squared error of the difference between the measured fluorescence data and calculated concentration by the conjugate gradient method in MATLAB, the rate constants in the 3-compartment model were determined. The accuracy of the fitting operation was confirmed with determination coefficient of 0.98. We could construct the 3-compartment pharmacokinetic model for canine using the measured talaporfin sodium fluorescence change from canine skin.

Proceedings Article | 8 February 2017 Paper

3-compartment dynamic model of talaporfin sodium pharmacokinetics in silico

Emiyu Ogawa, Yuko Uno, Keishi Ohtani, Sachio Maehara, Kentaro Imai, Shotaro Ono, Jitsuo Usuda, Tsunenori Arai

Proceedings Volume 10047, 100470Y (2017) https://doi.org/10.1117/12.2250716

KEYWORDS: Sodium, Plasma, Laser ablation, Laser irradiation, Luminescence, Data modeling, Oxygen, Fluorescence spectroscopy, Polymer optical fibers

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We studied a 3-compartment dynamic model of talaporfin sodium pharmacokinetics in silico. Drug distribution might change after intravenous injection from plasma to interstitial space and then into myocardial cells. We have developed a new cardiac ablation using photosensitization reaction with laser irradiation shortly after talaporfin sodium injection. We think that the major cell-killing factor in our cardiac ablation would be an oxidation by singlet oxygen produced in the interstitial space in myocardium with laser irradiation shortly after the photosensitizer administration. So that the talaporfin sodium concentration change in time in the interstitial space should be investigated. We constructed the pharmacokinetics dynamic model composed by 3-compartments, that is, plasma, interstitial space, and cell. We measured talaporfin sodium fluorescence time change in human skin by our developed fluorescence measurement system in vivo. Using the measured concentration data in plasma and skin in human, we verified the calculation accuracy of our in silico model. We compared the simulated transition tendency of talaporfin sodium concentration from interstitial space to cells in our in silico model with the reported uptake tendency using cultured myocardial cell. We identified the transition coefficients between plasma, interstitial space, and cell compartment, and metabolization coefficient from plasma by the fitting with measured data.

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