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Laboratory of Pharmaceutics

Laboratory of Pharmaceutics

Japanese

Quantitative understanding of the pharmacokinetics of drugs to facilitate drug development and to realize the proper use of drugs in the clinics
 

“Biopharmaceutics”is the research field to understand the mechanisms that govern the drug movement inside the body after drugs are administered. The pharmacokinetics (PK) of drugs in the body is determined by multiple processes of so-called "ADME"; Absorption, Distribution, Metabolism, and Excretion. In recent years, it has been elucidated that the ADME properties of drugs are dominated not only by their simple physicochemical properties but also by the functions of various PK-related molecules (metabolic enzymes, transporters) in a drug-selective manner. In addition, the functions of these molecules are modified by multiple intrinsic and extrinsic factors such as genetic polymorphisms, drug-drug interactions and pathophysiological conditions. Finally, various functional modifications of each function results in the inter-individual differences in the pharmacokinetics of drugs and subsequently their pharmacological/toxicological effects.
　We are studying to clarify the factors controlling pharmacokinetics and their quantitative contributions, and to predict in vivo pharmacokinetics based on the results of in vitro experiments.

Research Achievements

  • Original Articles
  • Lecture/Conference
  • Books/Publications

    • A general fluorescence off/on strategy for fluorogenic probes: Steric repulsion-induced twisted intramolecular charge transfer (sr-TICT).

    Kenjiro Hanaoka, Takayuki Ikeno, Shimpei Iwaki, Sayaka Deguchi, Kazuo Takayama, Hiroyuki Mizuguchi, Fumiya Tao, Nobuhiko Kojima, Hisashi Ohno, Eita Sasaki, Toru Komatsu, Tasuku Ueno, Kazuya Maeda, Hiroyuki Kusuhara, Yasuteru Urano
    Science advances, 10 (7) :eadi8847 (2024)
    https://10.1126/sciadv.adi8847

     

    Evaluation of the risk of diarrhea induced by epidermal growth factor receptor tyrosine kinase inhibitors with cultured intestinal stem cells originated from crypts in humans and monkeys.

    Yoshiki Hashimoto, Kazuya Maeda, Osamu Shimomura, Yoshihiro Miyazaki, Shinji Hashimoto, Akiko Moriyama, Tatsuya Oda, Hiroyuki Kusuhara
    Toxicology in vitro, 93 :105691 (2023)
    https://10.1016/j.tiv.2023.105691
     

    Model-based meta-analysis of ethnic differences and their variabilities in clearance of oral drugs classified by clearance mechanism.

    Hiromi Sato, Rika Marutani, Ryota Takaoka, Daniel Mori-Fegan, Xinying Wang, Kazuya Maeda, Hiroyuki Kusuhara, Hiroshi Suzuki, Hideki Yoshioka, Akihiro Hisaka
    CPT: pharmacometrics & systems pharmacology, 12 (8) :1132-42 (2023)
    https://10.1002/psp4.12980
     

    Quantitative prediction of intestinal absorption of drugs from in vitro study; utilization of differentiated intestinal epithelial cells derived from intestinal stem cells at crypts

    Kazuya Maeda.
    Drug Metabolism and Disposition: The Biological Fate of Chemicals, 51 (9) :1136-44 (2023)
    https://10.1124/dmd.122.000966
     

    Usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells for the prediction of intestinal drug absorption in humans

    Kazuyoshi Michiba,Kazuya Maeda,Osamu Shimomura,Yoshihiro Miyazaki,Shinji Hashimoto,Tatsuya Oda,Hiroyuki Kusuhara.
    Drug Metabolism and Disposition: The Biological Fate of Chemicals, 50 (3) :204-213 (2022)
    https://10.1124/dmd.121.000796
     

    Physiologically-based pharmacokinetic model-based translation of OATP1B-mediated drug–drug interactions from coproporphyrin I to probe drugs.

    Mochizuki T, Aoki Y, Yoshikado T, Yoshida K, Lai Y, Hirabayashi H, Yamaura Y, Rockich K, Taskar K, Takashima T, Chu X, Zamek-Gliszczynski MJ, Mao J,Maeda K, Furihata K, Sugiyama Y, Kusuhara H.
    Clin Trans Sci, 15 :1519-1531 (2022)
    https://doi.org/10.1111/cts.13272


    Frequency of null genotypes of glutathione S-transferase M1 and T1 in Japanese patients with drug-induced liver injury

    Maeda K, Takikawa H, Aiso M, Tsuji K, Kagawa T, Watanabe M, Sato K, Sakisaka S, Hiasa Y, Takei Y, Ohira H, Hashimoto E, Ayada M, Ikegami T, Arakawa N, Kusuhara H, Saito Y and Sugiyama Y..
    Hepatol Res, 52 (10) :882-887 (2022)
    https://doi.org/10.1111/hepr.13812


    64Cu-labeling of small extracellular vesicle surfaces via a cross-bridged macrocyclic chelator for pharmacokinetic study by positron emission tomography imaging

    Warashina S, Zouda M, Mohri K, Wada Y,Maeda K, Watanabe Y and Mukai H.
    Int J Pharmaceut, 624 :121968 (2022)
    https://doi.org/10.1016/j.ijpharm.2022.121968


    Construction of a culture protocol for functional bile canaliculi formation to apply human iPS cell-derived hepatocytes for cholestasis evaluation.

    Horiuchi S, Kuroda Y, Oyafuso R, Komizu Y, Takaki T,Maeda K, Ishida S..
    Sci. Rep., 12 :15192 (2022)
    https://doi.org/10.1038/s41598-022-19469-x


    Predicting Total Drug Clearance and Volumes of Distribution Using the Machine Learning-Mediated Multimodal Method through the Imputation of Various Nonclinical Data

    Iwata H, Matsuo T, Mamada H, Motomura T, Matsushita M, Fujiwara T,Maeda K, Handa K..
    J Chem Inf Model, 62 :4057-4065 (2022)
    https://doi.org/10.1021/acs.jcim.2c00318