Tomotaka Shingaki

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The sedating effect of first generation H1-antihistamines has been associated with their ability to penetrate the blood-brain barrier (BBB) and lack of efflux by P-glycoprotein (Pgp). Second generation H1-antihistamines are relatively free of sedation and their limited brain penetration has been suggested to arise from Pgp-mediated efflux. The objective of(More)
Brain tumors are one of the most lethal and difficult to treat. Their treatment is limited by the inadequate delivery of antitumor drugs to the tumor. In order to overcome this limitation, the possibility of the nose-brain direct transport pathway was evaluated using methotrexate (MTX) as a model antitumor agent. The direct transport of nasal MTX to the(More)
To develop potent drugs for oral use, information on their pharmacokinetic (PK) properties after oral administration is of great importance. We have recently reported the utility of positron emission tomography (PET) for the analysis of gastrointestinal (GI) absorption of radiolabeled compounds. In this study, PET image analysis was performed in rats using(More)
In order to develop a new positron emission tomography (PET) probe to study hepatobiliary transport mediated by the multi-drug and toxin extrusion transporter 1 (MATE1), (11)C-labelled metformin was synthesized and then evaluated as a PET probe. [(11)C]Metformin ([(11)C]4) was synthesized in three steps, from [(11)C]methyl iodide. Evaluation by small animal(More)
To evaluate the function of multidrug and toxin extrusion proteins (MATEs) using 11C-labeled metformin ([11C]metformin) by positron emission tomography (PET). PET was performed by intravenous bolus injection of [11C]metformin. Pyrimethamine at 0.5 and 5 mg/kg was intravenously administered to mice 30 min prior to the scan. Integration plot analysis was(More)
We developed a pravastatin derivative, sodium (3R,5R)-3,5-dihydroxy-7-((1S,2S,6S,8S)-6-hydroxy-2-methyl-8-((1-[(11)C]-(E)-2-methyl-but-2-enoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoate ([(11)C]DPV), as a positron emission tomography (PET) probe for noninvasive measurement of hepatobiliary transport, and conducted pharmacokinetic analysis in rats(More)
To dynamically analyze the processes of oral absorption and hepatobiliary distribution of telmisartan using positron emission tomography (PET). 11C-labeled telmisartan ([11C]TEL) was orally administered to rats with or without non-radiolabeled telmisartan (0.5, and 10 mg/kg). PET scanning of abdominal region and whole body was performed under conscious(More)
The purpose of the research is to evaluate the effect of acetazolamide (AZA), an inhibitor of the secretion of cerebrospinal fluid (CSF), on the direct drug transport from the nasal cavity to the CSF and the brain uptake of a model drug, 5-fluorouracil (5FU). 5FU was infused intravenously or perfused nasally in the presence and absence of intravenously(More)
Homeostasis is known to be involved in maintaining the optimal internal environment, helping to achieve the best performance of biological functions. At the same time, a deviation from optimal conditions often attenuates the performance of biological functions, and such restricted performance could be considered as individual fatigue, including physical and(More)
Our recent work suggested that intranasal coadministration with the cell-penetrating peptide (CPP) penetratin increased the brain distribution of the peptide drug insulin. The present study aimed to distinctly certify the ability of penetratin to facilitate the nose-to-brain delivery of insulin by quantitatively evaluating the distribution characteristics(More)