Article
Chemistry, Analytical
Abdulaziz Ahmed A. Saad, Fan Zhang, Moath Refat, Eyad Abdulwhab H. Mohammed, Mingkang Zhang, Yuyue Chen, Bandar Al Hamyari, Jameel Alafifi, Xin'an Wu
Summary: This study evaluated the effect of tamsulosin on the pharmacokinetics of metformin and found that tamsulosin can increase the systemic exposure and reduce excretion of metformin, possibly through inhibiting Oct2 and Mate1-mediated transport.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Tatsuya Kawasaki, Chisa Kaneko, Ryosuke Nakanishi, Yoshinori Moriyama, Tomohiro Nabekura
Summary: This study investigated the transport characteristics of amiloride by human MATE1 and found that MATE1 transported amiloride at an extracellular pH of 7.4, with saturated uptake and a bell-shaped pH profile. Additionally, the study discovered that pyrimethamine and fampridine exhibited strong inhibition on MATE1.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Naotoshi Yamamura, Tsuyoshi Mikkaichi, Ken-Ichi Itokawa, Misa Hoshi, Katja Damme, Stefanie Geigner, Christine Baumhauer
Summary: The aim of this study was to investigate the involvement of transporters in the renal secretion and absorption of mirogabalin. The results showed that mirogabalin is not a substrate of LAT1 but is associated with PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1, and/or MATE2-K.
Article
Toxicology
Guangju Wang, Yajuan Bi, Hui Xiong, Tongwei Bo, Lifeng Han, Lijun Zhou, Chunze Zhang, Youcai Zhang
Summary: Wedelolactone was identified as a competitive inhibitor of OCT2 and a noncompetitive inhibitor of MATE1, showing selectivity to inhibit OCT2 over MATE1. It alleviated cisplatin-induced cytotoxicity and acute kidney injury, suggesting its potential as a natural therapy for preventing cisplatin-induced nephrotoxicity. Further investigations on drug-drug interactions with WEL and substrates of OCT2 and/or MATE1 are warranted.
HUMAN & EXPERIMENTAL TOXICOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hong Yang, Shiwei Zhou, Dong Guo, Obinna N. Obianom, Qing Li, Yan Shu
Summary: The regulation of OCTs and MATEs remains poorly characterized. This study found that Cd2+ and candesartan may regulate OCTs and MATEs through different cellular trafficking pathways, significantly affecting drug disposition in the liver and kidney.
Article
Biochemistry & Molecular Biology
Ravi Ranjan Kumar, Ravi Jain, Sabir Akhtar, Nidha Parveen, Arabinda Ghosh, Veena Sharma, Shailja Singh
Summary: Vitamin B1 is essential for carbohydrate metabolism, and this study focuses on the enzyme Thiamine Pyrophosphokinase (TPK) and its role in Leishmania donovani, a parasite causing visceral leishmaniasis. In silico and biochemical experiments were conducted to identify and characterize LdTPK, and it was found that inhibiting LdTPK led to growth inhibition of the parasite. These findings suggest that LdTPK could be a potential target for the development of new anti-leishmanial agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Analytical
Jieyu Zhang, Yan Chen, Wenxiang Fan, Linnan Li, Yueming Ma, Zhengtao Wang, Rong Shi, Li Yang
Summary: The combined efficacy of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma is better than either herb alone, likely due to herb-herb interactions affecting potency. The active components in Plantago, geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA), and the active component in Coptis, berberine (BBR), were found to have competitive interactions driven by transporters rOCT2 and rMATE1. These interactions affect the transport and excretion of compounds and lead to changes in efficacy after co-administration.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Sebastian Kalamajski, Mi Huang, Jonathan Dalla-Riva, Maria Keller, Adem Y. Dawed, Ola Hansson, Ewan R. Pearson, Hindrik Mulder, Paul W. Franks
Summary: Common genetic variants in the SLC47A1 gene region were not significantly associated with metformin response in the study. Both genomic editing of rs2289669 or rs8065082 did not alter SLC47A1 expression or splicing, suggesting that the previously reported association between rs2289669-containing haploblock and metformin efficacy may not be explained by genetic variants within that region.
HUMAN MOLECULAR GENETICS
(2022)
Review
Pharmacology & Pharmacy
Abdulaziz Ahmed A. Saad, Fan Zhang, Eyad Abdulwhab H. Mohammed, Xin'an Wu
Summary: OCT2 and MATE1/2-K are crucial transporters in the kidneys that play a significant role in drug metabolism, therapeutic efficacy, and toxicity. Understanding the localization and functionality of these transporters is essential for preventing or enhancing drug-induced nephrotoxicity.
BIOLOGICAL & PHARMACEUTICAL BULLETIN
(2022)
Article
Biotechnology & Applied Microbiology
Alexandra Lukacova, Terezia Beck, Lenka Koptasikova, Ales Benda, Lucia Tomeckova, Miriam Trnikova, Diana Lihanova, Juergen Michael Steiner, Juraj Krajcovic, Matej Vesteg
Summary: Euglena gracilis, a freshwater protist, has various biotechnological applications and can be used for biofuel production, pharmaceuticals, and water remediation. However, its large-scale cultivation is limited by the high cost of adding vitamins B1 and B12 to the media. This study demonstrates that E. gracilis can be grown for long periods without the need for added vitamins B1 and B12 in a co-culture system involving the filamentous fungus Cladosporium westerdijkiae and the bacteria Lysinibacillus boronitolerans and Pseudobacillus badius. This finding significantly reduces the cultivation costs and the fungus C. westerdijkiae can be used for effective harvesting of E. gracilis through bioflocculation.
JOURNAL OF BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
O. Pavlova, S. Stepanenko, L. Chehivska, M. Sambon, L. Bettendorff, Yu Parkhomenko
Summary: Thiamine deficiency is closely related to oxidative stress and can affect the expression of thiamine metabolism proteins in the brain. Accumulation of ThDPox may serve as a potential marker of neurocellular dysfunction and thiamine metabolic state.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Chemistry, Multidisciplinary
Irene Hernandez-Lozano, Severin Mairinger, Michael Sauberer, Johann Stanek, Thomas Filip, Thomas Wanek, Giuliano Ciarimboli, Nicolas Tournier, Oliver Langer
Summary: The study investigated the role of cation transporters (OCTs, MATEs) in the renal and hepatic disposition of [C-11]metoclopramide in mice. Results showed that OCT1/2 contribute to kidney and liver uptake, while MATEs play a role in urinary excretion of the drug. Cation transporters may contribute to variability in metoclopramide pharmacokinetics and side effects.
PHARMACEUTICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Anne T. Nies, Jorg Koenig, Patrick Leuthold, Katja Damme, Stefan Winter, Mathias Haag, Satohiro Masuda, Stephan Kruck, Hannelore Daniel, Britta Spanier, Martin F. Fromm, Jens Bedke, Ken-Ichi Inui, Matthias Schwab, Elke Schaeffeler
Summary: This article introduces a new approach to identify transporter substrates, and successfully identifies novel drug substrates of the MATE1 transporter through metabolomic profiling, in silico ligand screening, and in vitro transport studies.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Simon Strobbe, Jana Verstraete, Christophe Stove, Dominique Van Der Straeten
Summary: Rice is a major food crop for half of the human population, but the starchy endosperm lacks essential micronutrients like thiamin. Through tissue-specific metabolic engineering, researchers were able to increase thiamin levels in polished rice by up to threefold, demonstrating the potential for future biofortification efforts.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
David A. Doetsch, Salim Ansari, Ole Jensen, Lukas Gebauer, Christof Duecker, Jurgen Brockmoeller, Alexandra Sachkova
Summary: This study characterized the substrate spectrum of a proton-organic cation (H + OC) antiporter, which is responsible for transporting organic cations through membranes. Using hCMEC/D3 cells as a model, the researchers examined the uptake of 72 drugs and identified 37 of them as good substrates of the H + OC antiporter. Further analysis showed that the substrates had specific characteristics, such as being more hydrophobic and having a lower topological polar surface area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Daiki Mori, Hiroo Ishida, Tadahaya Mizuno, Sojiro Kusumoto, Yusuke Kondo, Saki Izumi, Genki Nakata, Yoshitane Nozaki, Kazuya Maeda, Yasutsuna Sasaki, Ken-ichi Fujita, Hiroyuki Kusuhara
DRUG METABOLISM AND DISPOSITION
(2020)
Correction
Medicine, Research & Experimental
Saki Izumi, Yoshitane Nozaki, Hiroyuki Kusuhara, Koichiro Hotta, Toshiki Mochizuki, Takafumi Komori, Kazuya Maeda, Yuichi Sugiyama
MOLECULAR PHARMACEUTICS
(2020)
Article
Environmental Sciences
Takashi Kudo, Akihiro Inano, Sanae Midorikawa, Hitoshi Kubo, Kino Hayashi, Sawako Nakashima, Chizu Fukushima, Kazuya Maeda, Noboru Oriuchi, Shin Irie, Shunichi Yamashita, Hiroyuki Kusuhara
Article
Medicine, Research & Experimental
Takayoshi Nakaoka, Yuta Uetake, Ken-ichi Kaneko, Takashi Niwa, Hidenori Ochiai, Satsuki Irie, Yoshie Suezaki, Natsumi Otsuka, Emi Hayashinaka, Yasuhiro Wada, Yilong Cui, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama, Takamitsu Hosoya, Yasuyoshi Watanabe
MOLECULAR PHARMACEUTICS
(2020)
Article
Pharmacology & Pharmacy
Wooin Lee, Satoshi Koyama, Kiyoe Morita, Aya Kiriake, Ryota Kikuchi, Xiaoyan Chu, Nora Lee, Renato J. Scialis, Hong Shen, Emi Kimoto, Larry Tremaine, Naoki Ishiguro, Ralf Lotz, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama
Article
Pharmacology & Pharmacy
Kazuyoshi Michiba, Kazuya Maeda, Ko Kurimori, Tsuyoshi Enomoto, Osamu Shimomura, Tomoyo Takeuchi, Hiroyuki Nishiyama, Tatsuya Oda, Hiroyuki Kusuhara
Summary: This study characterized the functions of major intestinal uptake/efflux drug transporters in freshly isolated human jejunum sections using the Ussing chamber system. The findings showed a good correlation between the mucosal-to-serosal apparent permeability coefficient of various drugs and reported human FaFg values, highlighting the importance of intestinal uptake transporters in facilitating drug absorption in humans.
DRUG METABOLISM AND DISPOSITION
(2021)
Review
Pharmacology & Pharmacy
Tatsuki Mochizuki, Tadahaya Mizuno, Kazuya Maeda, Hiroyuki Kusuhara
Summary: Drug transporters play crucial roles in eliminating compounds from the blood, with genetic variation and drug-drug interactions being underlying factors for pharmacokinetic differences of transporter substrates. Some endogenous substrates of drug transporters have been identified as biomarkers to assess transporter activity differences. Metabolomic analysis is a promising approach for identifying endogenous substrates through metabolites.
DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Article
Chemistry, Medicinal
Takashi Yoshikado, Wooin Lee, Kota Toshimoto, Kiyoe Morita, Aya Kiriake, Xiaoyan Chu, Nora Lee, Emi Kimoto, Manthena V. S. Varma, Ryota Kikuchi, Renato J. Scialis, Hong Shen, Naoki Ishiguro, Ralf Lotz, Albert P. Li, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama
Summary: Hepatic uptake clearances of OATP1B substrates were compared between plated human hepatocytes (PHH) and suspended human hepatocytes (SHH), showing differences in uptake kinetics and cell-to-medium concentration ratios. PHH is useful for high-throughput evaluation of hepatic uptake/efflux clearances and Kp,Kuu, with caution needed for hydrophilic drugs with low uptake/cellular binding.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Cell & Tissue Engineering
Shinpei Yoshida, Takayuki Honjo, Keita Iino, Ryunosuke Ishibe, Sylvia Leo, Tomoka Shimada, Teruhiko Watanabe, Masaya Ishikawa, Kazuya Maeda, Hiroyuki Kusuhara, Nobuaki Shiraki, Shoen Kume
Summary: This study aimed to generate matured small intestinal cells mimicking human small intestine from human-induced pluripotent stem cells (iPSCs). By culturing iPSC-derived intestinal progenitor cells on collagen vitrigel membrane and treating with a simple maturation medium, enterocyte-like cells were successfully generated, showing potential applications in drug transport and metabolism studies.
Review
Pharmacology & Pharmacy
Kazuya Maeda, Akihiro Hisaka, Kiyomi Ito, Yoshiyuki Ohno, Akihiro Ishiguro, Reiko Sato, Naomi Nagai
Summary: This review highlights the importance of clinical drug interaction studies during new drug development and introduces the general procedures proposed in a recently updated Japanese guideline. Drugs are classified based on their clearance pathway and potential intensity according to systematic reviews of the literature, which is useful for managing drug interactions in clinical practice.
DRUG METABOLISM AND PHARMACOKINETICS
(2021)
Article
Materials Science, Biomaterials
Sayaka Deguchi, Masahiro Tsuda, Kaori Kosugi, Ayaka Sakamoto, Natsumi Mimura, Ryosuke Negoro, Emi Sano, Takuro Nobe, Kazuya Maeda, Hiroyuki Kusuhara, Hiroyuki Mizuguchi, Fumiyoshi Yamashita, Yu-suke Torisawa, Kazuo Takayama
Summary: The study evaluated drug absorption to the PDMS device and investigated the drug responsiveness of human hepatocytes cultured in the PDMS device. The absorption rates of different compounds to the PDMS device were measured and found to be correlated with their octanol/water distribution coefficient values. Furthermore, the hepatocyte-chips were used to examine the response to drugs typically used to evaluate hepatic functions.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2021)
Article
Pharmacology & Pharmacy
Kazuyoshi Michiba, Kazuya Maeda, Osamu Shimomura, Yoshihiro Miyazaki, Shinji Hashimoto, Tatsuya Oda, Hiroyuki Kusuhara
Summary: This study has demonstrated the usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells as an in vitro model for studying the impact of intestinal drug-metabolizing enzymes and transporters on substrate drugs' absorption in humans. The model was able to maintain the functions of major intestinal drug-metabolizing enzymes and transporters. It could be used for quantitative evaluation of the impact of these enzymes and transporters on drug absorption.
DRUG METABOLISM AND DISPOSITION
(2022)
Review
Pharmacology & Pharmacy
Yoshiki Hashimoto, Kazuyoshi Michiba, Kazuya Maeda, Hiroyuki Kusuhara
Summary: Efflux transport systems play a crucial role in inhibiting the absorption and distribution of drugs in the human body, with genetic variations and coadministered drugs affecting transporter expression and function. Utilizing in vitro experimental tools and mathematical modeling allows for accurate prediction of drug pharmacokinetics.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Tatsuki Mochizuki, Maciej J. Zamek-Gliszczynski, Kenta Yoshida, Jialin Mao, Kunal Taskar, Hideki Hirabayashi, Xiaoyan Chu, Yurong Lai, Tadayuki Takashima, Kevin Rockich, Yoshiyuki Yamaura, Kaku Fujiwara, Tadahaya Mizuno, Kazuya Maeda, Kenichi Furihata, Yuichi Sugiyama, Hiroyuki Kusuhara
Summary: This study assessed the quantitative performance of endogenous biomarkers for OATP1B1/1B3-mediated drug-drug interactions, with CP-I's AUCR and CmaxR showing high correlation with CysA AUC. The findings provide valuable information for accurate DDI predictions and enhance understanding of interindividual variability in DDI magnitude.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Tatsuki Mochizuki, Yasunori Aoki, Takashi Yoshikado, Kenta Yoshida, Yurong Lai, Hideki Hirabayashi, Yoshiyuki Yamaura, Kevin Rockich, Kunal Taskar, Tadayuki Takashima, Xiaoyan Chu, Maciej J. Zamek-Gliszczynski, Jialin Mao, Kazuya Maeda, Kenichi Furihata, Yuichi Sugiyama, Hiroyuki Kusuhara
Summary: In this study, a physiologically-based pharmacokinetic (PBPK) model analysis was performed to interpret clinical drug-drug interaction (DDI) data, and the results suggest that PBPK model analysis of CP-I is a promising translational approach to predict OATP1B-mediated DDIs in drug development.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)