Yajima, Kodai

写真a

Affiliation

Faculty of Pharmacy, Department of Pharmacy 統合臨床薬理学講座 (Shiba-Kyoritsu)

Position

Research Associate/Assistant Professor/Instructor
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Academic Background 【 Display / hide 】

  • 2012.04
    -
    2018.03

    Keio University, 薬学部, 薬学科

    University, Graduated

  • 2019.04
    -
    2024.03

    慶應義塾大学大学院, 薬学研究科, 薬学専攻

    Graduate School, Completed, Doctoral course

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Academic Degrees 【 Display / hide 】

  • 博士（薬学）, Keio University, Coursework, 2024.03

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Licenses and Qualifications 【 Display / hide 】

  • 薬剤師, 2018.04

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Research Areas 【 Display / hide 】

  • Life Science / Clinical pharmacy (薬物動態学)

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Research Keywords 【 Display / hide 】

  • トランスポーター、抗体医薬品

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Papers 【 Display / hide 】

  • Population pharmacokinetic analysis of bevacizumab in Japanese cancer patients with proteinuria: a prospective cohort study

    Masuda T., Funakoshi T., Horimatsu T., Masui S., Hira D., Inoue M., Yajima K., Nakagawa S., Ikemi Y., Hamanishi J., Takai A., Yamamoto S., Matsubara T., Mandai M., Seno H., Yanagita M., Muto M., Terada T., Yonezawa A.

    Cancer Chemotherapy and Pharmacology 95 ( 1 )  2025.12

    ISSN  03445704

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    Purpose: Bevacizumab (BV) is an effective therapeutic antibody utilized in various cancers. Serum BV concentration can be a factor that potentially affects its therapeutic efficacy. Although proteinuria could affect BV pharmacokinetics, its influence was not evaluated in the previous population pharmacokinetic (PopPK) studies. Because BV can cause proteinuria as an adverse event, the present study aimed to develop a PopPK model in patients with proteinuria and to evaluate the influence of proteinuria on BV pharmacokinetics. Methods: This prospective cohort study enrolled 70 Japanese cancer patients newly starting BV, and 368 concentration samples from these patients were analyzed. Serum BV concentrations were measured at several time points including at the onset of proteinuria. PopPK analysis was conducted using a non-linear mixed-effects modeling program. A two-compartment model was used to estimate total body clearance (CL). Results: Serum BV concentrations divided by the dose per body weight and dosing interval tended to be lower in patients with higher urinary protein to creatinine ratio (UPCR). The covariate analysis showed that increasing BV CL was associated with decreasing serum albumin concentration and increasing body weight and UPCR. The simulated median trough concentrations of BV in patients with Common Terminology Criteria for Adverse Events grades 1, 2, and 3 proteinuria were decreased by 12.0%, 20.6%, and 31.5%, respectively, compared to those in patients with grade 0. Conclusion: We successfully established a PopPK model incorporating UPCR to predict serum BV concentrations in patients with proteinuria. Our study provides additional insights to better understand BV pharmacokinetics.

  • Determination of single-molecule transport activity of OATP2B1 by measuring the number of transporter molecules using electrophysiological approach

    Yajima K., Akiyoshi T., Sakamoto K., Suzuki Y., Oka T., Imaoka A., Yamamura H., Kurokawa J., Ohtani H.

    Journal of Pharmacological Sciences (Journal of Pharmacological Sciences)  153 ( 3 ) 153 - 160 2023.11

    Research paper (scientific journal), Lead author, Accepted,  ISSN  13478613

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    Transporter-mediated clearance is determined by two factors, its single-molecule clearance, and expression level. However, no reliable method has been developed to evaluate them separately. This study aimed to develop a reliable method for evaluating the single-molecule activity of membrane transporters, such as organic anion transporting polypeptide (OATP) 2B1. HEK293 cells that co-expressed large conductance calcium-activated potassium (BK) channel and OATP2B1 were established and used for the following experiments. i) BK channel-mediated whole-cell conductance was measured using patch-clamp technique and divided by its unitary conductance to estimate the number of channels on plasma membrane (QI). ii) Using plasma membrane fraction, quantitative targeted absolute proteomics determined the stoichiometric ratio (ρ) of OATP2B1 to BK channel. iii) The uptake of estrone 3-sulfate was evaluated to calculate the Michaelis constant and uptake clearance (CL) per cell. Single-molecule clearance (CLint) was calculated by dividing CL by QI·ρ. QI and ρ values were estimated to be 916 and 2.16, respectively, yielding CLint of 5.23 fL/min/molecule. We successfully developed a novel method to reliably measure the single-molecule activity of a transporter, which could be used to evaluate the influences of factors such as genetic variations and post-translational modifications on the intrinsic activity of transporters.

  • The Effects of Jabara Juice on the Intestinal Permeation of Fexofenadine

    Han H., Akiyoshi T., Morita T., Tsuchitani T., Nabeta M., Yajima K., Imaoka A., Ohtani H.

    Biological and Pharmaceutical Bulletin (Biological and Pharmaceutical Bulletin)  46 ( 12 ) 1745 - 1752 2023

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  09186158

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    Jabara juice and its component narirutin inhibit the activity of organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1, which are considered to play significant roles in the intestinal absorption of fexofenadine. In this study, we investigated the effects of jabara juice on the intestinal absorption of fexofenadine in mice and the inhibitory effects of jabara juice and narirutin on the permeation of fexofenadine using Caco-2 cell monolayers and LLC-GA5-COL300 cell monolayers. In the in vivo study, the area under the plasma concentration–time curve (AUC) of fexofenadine in mice was increased 1.8-fold by jabara juice. In the permeation study, 5% jabara juice significantly decreased the efflux ratio (ER) of fexofenadine for Caco-2 monolayers. Furthermore, the ERs of fexofenadine and digoxin, which is a typical substrate of P-glycoprotein (P-gp), for LLC-GA5-COL300 cell monolayers were decreased in a concentration-dependent manner by jabara juice extract, suggesting that jabara juice may increase the intestinal absorption of fexofenadine by inhibiting P-gp, rather than by narirutin inhibiting OATPs. The present study showed that jabara juice increases the intestinal absorption of fexofenadine both in vivo and in vitro. The intestinal absorption of fexofenadine may be altered by the co-administration of jabara juice in the clinical setting.

  • Comparison of the transport kinetics of fexofenadine and its pH dependency among OATP1A2 genetic variants

    Han H., Akiyoshi T., Morita T., Kataoka H., Katayama K., Yajima K., Imaoka A., Ohtani H.

    Drug Metabolism and Pharmacokinetics (Drug Metabolism and Pharmacokinetics)  47 2022.12

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  13474367

    　View Summary

    Little is known about the influence of non-synonymous genetic variations in the organic anion-transporting polypeptide (OATP) 1A2 on the transport kinetics of its substrate fexofenadine. Moreover, the pH-dependency of fexofenadine uptake also remains unclear. This study aimed to evaluate the effects of genetic variants (Ile13Thr, Asn128Tyr, Glu172Asp, Ala187Thr, and Thr668Ser) on the OATP1A2-mediated uptake of fexofenadine at pH 6.3 and 7.4 and compare the pH dependency of OATP1A2-mediated uptake of fexofenadine and estrone 3-sulfate. The uptake clearances of 0.3 μM and 300 μM fexofenadine were compared with those of 0.3 μM and 300 μM estrone 3-sulfate at pH 6.3 and 7.4. Among the six variants examined, the Thr668Ser variant showed the highest fexofenadine uptake clearance (Vmax/Km); i.e., 4.53- and 6.28-fold higher uptake clearance than the wild type at pH 6.3 and 7.4, respectively. All variants exhibited significantly higher fexofenadine uptake at pH 6.3 than at pH 7.4. Compared with estrone 3-sulfate uptake, the uptake of 0.3 μM fexofenadine was less sensitive to pH. Our findings suggest that genetic variations in OATP1A2 may lead to altered intestinal absorption of fexofenadine, such as increased absorption in subjects bearing the Thr668Ser variant, which showed higher uptake activity.

  • Comparison of the inhibitory properties of the fruit component naringenin and its glycosides against OATP1A2 genetic variants

    Araki N., Morita T., Akiyoshi T., Kataoka H., Yajima K., Katayama K., Imaoka A., Ohtani H.

    Drug Metabolism and Pharmacokinetics (Drug Metabolism and Pharmacokinetics)  46 2022.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  13474367

    　View Summary

    Non-synonymous genetic variants of organic anion-transporting polypeptide (OATP) 1A2 with altered transport activity have been identified. Naringin and narirutin, which are found in grapefruit, and their aglycon naringenin inhibit OATP1A2. However, their inhibitory effects on OATP1A2 variants have not been investigated, nor has the influence of their molecular structure, such as the number of sugar moieties, on their inhibitory potency. This study aimed to investigate the inhibitory effects of naringenin, its monosaccharide glycoside prunin, and its disaccharide glycosides naringin and narirutin on fexofenadine (FEX) uptake by OATP1A2 variants (Ile13Thr, Asn128Tyr, Ala187Thr, and Thr668Ser). Naringin, narirutin, and prunin inhibited FEX (0.3 μM) uptake by all of the examined OATP1A2 variants in a concentration-dependent manner. Compared with those for the wild type, the inhibition constants (Ki) of naringin, narirutin, and prunin for the Ala187Thr variant were significantly increased by 3.36-fold, 7.55-fold, and 10.6-fold, respectively. Naringenin inhibited all of the OATP1A2 variants, except Ala187Thr, concentration-dependently. The order of inhibitory potency was as follows for all variants: aglycone > monosaccharide glycoside > disaccharide glycosides. These results suggest that the Ala187Thr variant is less vulnerable to inhibition by naringenin and its glycosides. Moreover, greater glycosylation of naringenin reduces its inhibitory potency against OATP1A2.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Presentations 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Exploring immunogenicity factors of antibody drug through understanding drug structures

    2024.07
    -
    2026.03

    研究活動スタート支援, Principal investigator

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Courses Taught 【 Display / hide 】

  • STUDY OF MAJOR FIELD(INTEGRATIVE CLINICAL PHARMACOLOGY)

    2025

  • SEMINAR(INTEGRATIVE CLINICAL PHARMACOLOGY)

    2025

  • RESEARCH FOR BACHELOR'S THESIS 1

    2025

  • PRE-CLINICAL TRAINING FOR HOSPITAL & COMMUNITY PHARMACY

    2025

  • PHARMACEUTICAL-ENGLISH SEMINAR

    2025

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Memberships in Academic Societies 【 Display / hide 】

  • 日本医療薬学会, 

    2024.04
    -
    Present
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