Zakoji, Nobuyuki Tajima, Kosuke Yoneyama, Daisuke Akanuma, Shin-Ichi Kubo, Yoshiyuki Hosoya, Ken-Ichi
Published in
Drug metabolism and pharmacokinetics
The retinal pericytes contribute to the supply of collagen to the basement membrane, and thus, form the structural support of the blood-retinal barrier. Since l-proline (L-Pro) is a major component of collagen, the uptake of L-Pro is an important process for the synthesis of collagen. This study was aimed to elucidate L-Pro transport mechanism(s) i...
Kabeya, Tomoki Mima, Shinji Imakura, Yuki Miyashita, Toshihide Ogura, Izumi Yamada, Tadanori Yasujima, Tomoya Yuasa, Hiroaki Iwao, Takahiro Matsunaga, Tamihide
...
Published in
Drug metabolism and pharmacokinetics
To develop a novel intestinal drug absorption system using intestinal epithelial cells derived from human induced pluripotent stem (iPS) cells, the cells must possess sufficient pharmacokinetic functions. However, the CYP3A4/5 activities of human iPS cell-derived small intestinal epithelial cells prepared using conventional differentiation methods ...
Nakanishi, Yasuharu Uno, Yasuhiro Yamazaki, Hiroshi
Published in
Drug metabolism and pharmacokinetics
The cynomolgus macaque is a nonhuman primate species that is often used in drug metabolism studies during drug development. However, the localization of UDP-glucuronosyltransferases (UGTs), essential drug-metabolizing enzymes, has not been fully investigated in the liver and small intestine of cynomolgus macaques. In this study, UGT activities were...
Dionisio, Leonardo Shimizu, Makiko Stupniki, Sofia Oyama, Saki Aztiria, Eugenio Alda, Maximiliano Yamazaki, Hiroshi Spitzmaul, Guillermo
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Drug metabolism and pharmacokinetics
Flavin-containing monooxygenase 3 (FMO3) is a polymorphic drug metabolizing enzyme associated with the genetic disorder trimethylaminuria. We phenotyped a white Argentinian 11-year-old girl by medical sensory evaluation. After pedigree analysis with her brother and parents, this proband showed to harbor a new allele p.(P73L; E158K; E308G) FMO3 in t...
Tamaki, Shun Imaishi, Hiromasa
Published in
Drug metabolism and pharmacokinetics
Human cytochrome P450 (or CYP) inhibition rates were investigated in sera from high fat diet (HFD)-induced type 2 diabetes (T2D), T2D recovered, and asymptomatic mice models to verify whether P450 inhibition assays could be used for the detection of disease, evaluation of therapeutic effect, and early diagnosis of T2D. In T2D mice, the blood glucos...
Wang, Ting Babusis, Darius Park, Yeojin Niu, Congrong Kim, Cynthia Zhao, Xiaofeng Lu, Bing Ma, Bin Muench, Robert C Sperger, Diana
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Published in
Drug metabolism and pharmacokinetics
Sofosbuvir (SOF) is a nucleotide prodrug which has been used as a backbone for the clinical treatment of hepatitis C viral infection. Because sofosbuvir undergoes complex first pass metabolism, including metabolic activation to form its pharmacologically active triphosphate (GS-331007-TP) to inhibit the viral RNA polymerase in the liver, it is diff...
Uno, Yasuhiro Murayama, Norie Yamazaki, Hiroshi
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Drug metabolism and pharmacokinetics
The cynomolgus macaque, partly due to its evolutionary closeness to humans, is an important nonhuman primate species used in drug metabolism studies. In humans, expressions of cytochromes P450 (P450s), including the important drug-metabolizing enzyme P450 3A4, are affected by various cytokines. However, this phenomenon has not been fully investigat...
Mizoi, Kenta Hosono, Mayu Kojima, Hajime Ogihara, Takuo
Published in
Drug metabolism and pharmacokinetics
Some drugs induce cytochrome P450s (CYPs), and thus may cause increased metabolic toxicity from concomitantly administered agents. Hence, we need a means of evaluating the potential of compounds to cause drug-induced liver injury (DILI) under conditions where inducers of CYP1A2 are present. Here, we present a system for evaluating CYP1A2-mediated m...
Morita, Tokio Akiyoshi, Takeshi Sato, Ryo Katayama, Kazuhiro Yajima, Kodai Kataoka, Hiroki Imaoka, Ayuko Sugimoto, Yoshikazu Ohtani, Hisakazu
Published in
Drug metabolism and pharmacokinetics
Organic anion-transporting polypeptide (OATP) 1A2 is expressed on the apical sides of intestinal and renal epithelial cells and considered to be involved in the intestinal absorption and renal reabsorption of drugs. Although the transport activity of OATP1A2 is considered to be pH-dependent, the effects of pH on its kinetic parameters and on the po...
Tohkin, Masahiro Saito, Yoshiro Yagi, Satomi Asano, Kunihito Maekawa, Keiko Osabe, Makoto Iida, Shinsuke Miyata, Naoki
Published in
Drug metabolism and pharmacokinetics
Recently, genomic biomarkers have been widely used clinically for prediction of the efficacy and safety of pharmacotherapy and diagnosis and prognosis of pathological conditions. Therefore, genomic biomarkers are anticipated to accelerate not only precision medicine for pharmacotherapy but also development of molecularly targeted drugs. Because the...
