Yoon‐Jee Chae

Woosuk University

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Kyeong‐Ryoon Lee

Korea Research Institute of Bioscience and Biotechnology

Suk‐Jae Chung

Seoul National University

Ji‐Eun Chang

Dongduk Women's University

Han‐Joo Maeng

Gachon University

Tae‐Sung Koo

Chungnam National University

Min‐Soo Kim

University of Waterloo

Kwang‐Hee Shin

Kyungpook National University

Dae‐Duk Kim

Seoul National University

Yoo-Kyung Song

Chong Kun Dang Bio (South Korea)

Jong‐Hwa Lee

Chosun University

Cooperative Institutions

Seoul National University

Chungnam National University

Korea Research Institute of Bioscience and Biotechnology

Korea Research Institute of Chemical Technology

Gachon University

Daewoong Pharmaceutical (South Korea)

Yonsei University

Sungkyunkwan University

Woosuk University

Pusan National University

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Findings on In Vitro Transporter-Mediated Drug Interactions and Their Follow-Up Actions for Labeling: Analysis of Drugs Approved by US FDA between 2017 and 2021

Pharmaceutics (2022)

Kyeong‐Ryoon Lee Ji‐Eun Chang Jongmin Yoon Hyojeong Jin Yoon‐Jee Chae

Understanding possible follow-up actions on in vitro findings helps determine the necessity of labeling for drug interactions. We analyzed information for in vitro findings on transporter-mediated interactions of drugs approved by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research for the last five years (i.e., 2017-2021) and their follow-up actions for labeling. Higher R values than the pre-defined cut-off were observed with 3.7-39.1% inhibitor drugs in a simple prediction. Among these drugs, 16-41.7% were labeled with their potential drug interactions, while results of supporting studies or scientific rationales were submitted for the other drugs leading to no interaction labeling. In vitro transporter substrates were reported with 1.7-67.6% of drugs. The interaction labels for these substrate drugs were observed in up to 40% of drugs, while the other drugs were not labeled on the drug interactions with claims for their low interaction potential, evidenced by clinical studies or scientific rationales. The systematic and comprehensive analysis in this study will provide insight into the management of in vitro findings for transporter substrate or inhibitor drugs.

Drug-drug interaction

10.3390/pharmaceutics14102078

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Citations (2)

The In Vitro and In Vivo Anticancer Effect of Photomed for Photodynamic Therapy: Comparison with Photofrin and Radachlorin

Current Issues in Molecular Biology (2023)

Ji‐Eun Kim JoHyun Kim Heewon Yoon Yoon‐Jee Chae Kiyon Rhew

To overcome the limitation of conventional cancer treatments, photodynamic therapy (PDT) has been introduced as another treatment option. PDT provides a non-invasive, non-surgical way with reduced toxicity. To improve the antitumor efficacy of PDT, we synthesized a novel photosensitizer, a 3-substituted methyl pyropheophorbide-a derivative (Photomed). The purpose of the study was to evaluate the antitumor effect of PDT with Photomed comparing with the clinically approved photosensitizers Photofrin and Radachlorin. The cytotoxicity assay against SCC VII cells (murine squamous cell carcinoma) was performed to determine whether Photomed is safe without PDT and whether Photomed is effective against cancer cells with PDT. An in vivo anticancer efficacy study was also performed using SCC VII tumor-bearing mice. The mice were divided into small-tumor and large-tumor groups to identify whether Photomed-induced PDT is effective for not only small tumors but also large tumors. From in vitro and in vivo studies, Photomed was confirmed to be (1) a safe photosensitizer without laser irradiation, (2) the most effective photosensitizer with PDT against cancers compared to Photofrin and Radachlorin and (3) effective with PDT in treating not only small tumors but also large tumors. In conclusion, Photomed may contribute as a novel, potential photosensitizer for use in PDT cancer treatment.

10.3390/cimb45030162

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Citations (10)

QUANTIFICATION OF CILNIDIPINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY

Journal of Liquid Chromatography &amp Related Technologies (2012)

Kyeong‐Ryoon Lee Yoon‐Jee Chae Jong‐Hwa Lee Dae‐Duk Kim Saeho Chong

A liquid chromatography-mass spectrometry (LC-MS) assay was developed and validated for the quantification of cilnidipine, a calcium channel antagonist, in human plasma. Plasma samples were processed by liquid-liquid extraction and the analyte, along with nimodipine (an internal standard), and analyzed using selected ion monitoring (SIM) for detection. The absolute extraction recovery was determined to be not less than 89.1% for various concentrations. The detector response was specific and linear for cilnidipine concentrations in the range of 0.5–50 ng/mL. Validation parameters, including inter-/intra-day precision and accuracy, were found to be within the acceptance criteria for assay validation guidelines. The analyte was stable under a variety of processing and handling conditions. Cilnidipine levels were readily measured in plasma samples up to 10 hr after an oral administration of 10 mg of a cilnidipine formulation in humans, suggesting that the assay can be used in routine analyses.

Nimodipine

10.1080/10826076.2011.597078

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Citations (18)

Effect of ingestion methods of jellies for oral administration on drug absorption in beagle dogs

Journal of Pharmaceutical Investigation (2021)

Kyoung Hee Han Joong-Won Jeon Yoon‐Jee Chae Mi-Kyung Lee

Beagle

Drug Administration

10.1007/s40005-021-00535-x

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Development of Physiologically Based Pharmacokinetic Model for Orally Administered Fexuprazan in Humans

Pharmaceutics (2021)

Yoo‐Seong Jeong Min‐Soo Kim Nora Lee Areum Lee Yoon‐Jee Chae

Fexuprazan is a new drug candidate in the potassium-competitive acid blocker (P-CAB) family. As proton pump inhibitors (PPIs), P-CABs inhibit gastric acid secretion and can be used to treat gastric acid-related disorders such as gastroesophageal reflux disease (GERD). Physiologically based pharmacokinetic (PBPK) models predict drug interactions as pharmacokinetic profiles in biological matrices can be mechanistically simulated. Here, we propose an optimized and validated PBPK model for fexuprazan by integrating in vitro, in vivo, and in silico data. The extent of fexuprazan tissue distribution in humans was predicted using tissue-to-plasma partition coefficients in rats and the allometric relationships of fexuprazan distribution volumes (VSS) among preclinical species. Urinary fexuprazan excretion was minimal (0.29–2.02%), and this drug was eliminated primarily by the liver and metabolite formation. The fraction absorbed (Fa) of 0.761, estimated from the PBPK modeling, was consistent with the physicochemical properties of fexuprazan, including its in vitro solubility and permeability. The predicted oral bioavailability of fexuprazan (38.4–38.6%) was within the range of the preclinical datasets. The Cmax, AUClast, and time-concentration profiles predicted by the PBPK model established by the learning set were accurately predicted for the validation sets.

ADME

Pharmacodynamics

10.3390/pharmaceutics13060813

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Citations (14)

Pharmacokinetics of lurasidone, a novel atypical anti-psychotic drug, in rats

Xenobiotica (2011)

Kyeong‐Ryoon Lee Yoon‐Jee Chae Tae‐Sung Koo

This study aimed to characterise the pharmacokinetics of lurasidone, a new atypical anti-psychotic drug, in rats after intravenous and oral administration at dose range 0.5–2.5 and 2.5–10 mg/kg, respectively. Moreover, tissue distribution, liver microsomal stability and plasma protein binding were estimated.

Lurasidone

10.3109/00498254.2011.603388

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Citations (27)

Investigation of N-Acetyltransferase 2-Mediated Drug Interactions of Amifampridine: In Vitro and In Vivo Evidence of Drug Interactions with Acetaminophen

Pharmaceutics (2023)

Yeo-Dim Park Yoon‐Jee Chae Han‐Joo Maeng

Amifampridine is a drug used for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) and was approved by the Food and Drug Administration (FDA) of the United States (US) in 2018. It is mainly metabolized by N-acetyltransferase 2 (NAT2); however, investigations of NAT2-mediated drug interactions with amifampridine have rarely been reported. In this study, we investigated the effects of acetaminophen, a NAT2 inhibitor, on the pharmacokinetics of amifampridine using in vitro and in vivo systems. Acetaminophen strongly inhibits the formation of 3-N-acetylamifmapridine from amifampridine in the rat liver S9 fraction in a mixed inhibitory manner. When rats were pretreated with acetaminophen (100 mg/kg), the systemic exposure to amifampridine significantly increased and the ratio of the area under the plasma concentration-time curve for 3-N-acetylamifampridine to amifampridine (AUCm/AUCp) decreased, likely due to the inhibition of NAT2 by acetaminophen. The urinary excretion and the amount of amifampridine distributed to the tissues also increased after acetaminophen administration, whereas the renal clearance and tissue partition coefficient (Kp) values in most tissues remained unchanged. Collectively, co-administration of acetaminophen with amifampridine may lead to relevant drug interactions; thus, care should be taken during co-administration.

Acetaminophen

10.3390/pharmaceutics15051471

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Citations (0)

Interactions of bosutinib with drug transporters: In vitro and In vivo inhibition of organic cation transporter 2, multidrug and toxin extrusion protein 1, and breast cancer resistance protein by bosutinib

Biomedicine & Pharmacotherapy (2024)

Minji Kang Min Ju Kim Yunjin Seol Ji‐Eun Chang Kyeong‐Ryoon Lee

Bosutinib

Abcg2

P-glycoprotein

10.1016/j.biopha.2024.117114

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