平成 28 年
「生体分子コバレント修飾の革新的解析拠点形成」プロジェクト研究成果
研究室名： 薬物動態学 研究室【原著】
Shimada T, Takenaka S, Murayama N, Kramlinger V M, Kim J-H, Kim D,Foroozesh M K, Yamazaki H, Guengerich F P, and Komori M. Oxidation of pyrene,
1-hydroxypyrene, 1-nitropyrene, and 1-acetylpyrene by human cytochrome P450
2A13. Xenobiotica, 46, 211-224, 2016. [PubMed]Uehara S, Inoue T, Utoh M, Toda A, Shimizu M, Uno Y, Sasaki E, and Yamazaki
H. Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes,caffeine, warfarin, omeprazole, metoprolol, and midazolam, in commonmarmosets (Callithrix jacchus). Xenobiotica, 46, 163-168, 2016. [PubMed]

Uno Y, Yamazaki H. Development of a genotyping tool for a functionally relevant
CYP2C19 allele (Phe100Asn, Ala103Val, Ile112Leu) in cynomolgus macaques,J.Vet.Med.Sci., 78, 147-148, 2016. [Link]

Sekiguchi K, Kanazu T, Murayama N, Yamazaki H, and Yamaguchi T. In vitro
inhibition and enhancement of liver microsomal S-777469 metabolism by longchain fatty acids and serum albumin: insight into in vitro and in vivo discrepancyof metabolite formation in humans. Xenobiotica, 46, 495-502, 2016. [PubMed]Uehara S, Uno Y, Inoue T, Suzuki T, Utoh M, Sasaki E, and Yamazaki H. Caffeine
7-N-demethylation and C-8-oxidation mediated by liver microsomal cytochrome
P450 enzymes in common marmosets. Xenobiotica, 46, 573-578, 2016. [PubMed]Uehara S, Uno Y, Inoue T, Sasaki E, and Yamazaki H. Molecular cloning, tissue
distribution, and functional characterization of marmoset cytochrome P450 1A1,1A2, and 1B1. Drug Metab. Dispos, 44，8-15, 2016. [PubMed]Okubo M, Narita M, Murayama N, Akimoto Y, Goto A, and Yamazaki H.
Individual differences in in vitro and in vivo metabolic clearances of the
antipsychotic drug olanzapine from non-smoking and smoking Japanese subjects
genotyped for cytochrome P450 2D6 and flavin-containing monooxygenase 3.
Hum.Psychopharmacol.Clin.Exp., 31, 83-92, 2016. [PubMed]Okubo M, Morita S, Murayama N, Akimoto Y, Goto A, and Yamazaki H.
Individual differences in in vitro and in vivo metabolic clearances of antipsychotic
risperidone from Japanese subjects genotyped for cytochrome P450 2D6 and 3A5.
Hum.Psychopharmacol.Clin.Exp., 31, 93-102, 2016. [PubMed]

Kazuki Y, Akita M, Kobayashi K, Osaki M, Satoh D, Abe S, Takehara S, Kazuki
K, Yamazaki H, Kamataki T, and Oshimura M. Thalidomide-induced limb
abnormalities in a humanized CYP3A mouse model. Sci.Rep., 6, 21419, 2016.
[Link]

Uehara, S., Uno, Y., Yuki, Y., Inoue, T., Sasaki, E., and Yamazaki, H. A newmarmoset P450 4F12 enzyme expressed in small intestines and livers efficiently
metabolizes an anti-histaminic drug ebastine. Drug Metab. Dispos., 44, 833-841,
2016. [Link]

Sawada G, Niida A, Uchi R, Hirata H, Shimamura T, Suzuki Y, Shiraishi Y, Chiba
K, Imoto S, Takahashi Y, Iwaya T, Hayashi T, Takai H, Kawasaki Y, Matsukawa
T, Eguchi H, Sugimachi K, Tanaka F, Suzuki H., Yamamoto K, Ishii H, Shimizu
M, Yamazaki H, Yamazaki M, Tachimori Y, Kajiyama Y, Natsugoe S, Fujita H,Mafune K, Tanaka Y, Kelsell D P, Scott C A, Tsuji S, Yachida S, Shibata T, Sugano
S, Doki Y, Akiyama T, Aburatani H, Ogawa S, Miyano S, Mori M, and Mimori K.
Genomic landscape of esophageal squamous cell carcinoma in a Japanese
population. Gastroenterology, 150,1171-1182,2016. [PubMed]

Sakai C, Iwano S, Shimizu M, Onodera J, Uchida M, Sakurada E, Yamazaki Y,Asaoka Y, Imura N, Uno Y, Murayama N, Hayashi R, Yamazaki H, and Miyamoto
Y. Analysis of gene expression for microminipig liver transcriptomes using
parallel long-read technology and short-read sequencing, Biopharm. DrugDispos., 37, 220-232, 2016. [PubMed]

Shida S and Yamazaki H. Human plasma concentrations of five cytochrome P450
probes extrapolated from pharmacokinetics in dogs and minipigs using
physiologically based pharmacokinetic modeling. Xenobiotica, 46, 759-764, 2016.
[PubMed]Sugiyama I, Murayama N, Kuroki A, Kota J, Iwano S, Yamazaki H, and HirotaT. Evaluation of cytochrome P450 inductions by anti-epileptic drug oxcarbazepine,10-hydroxyoxcarbazepine, and carbamazepine using human hepatocytes andHepaRG cells. Xenobiotica, 46, 765-774, 2016. [PubMed]

Shimada T, Takenaka S, Kakimoto K, Murayama N, Lim Y-R, Kim D, Foroozesh
M, Yamazaki H, Guengerich F P, and Komori M. Structure-function studies ofnaphthalene, phenanthrene, biphenyl, and their alkynyl derivatives ininteraction with and oxidation by cytochromes P450 2A13 and 2A6. Chem. Res.
Toxicol., 29, 1029-1040, 2016. [ACS]Uehara S, Uno Y, Inoue T, Kawano M, Shimizu M, Toda A, Utoh M, Sasaki E andYamazaki, H. Individual differences in metabolic clearance of S-warfarinefficiently mediated by polymorphic marmoset cytochrome P450 2C19 in livers.
Drug Metab. Dispos., 44, 911-915, 2016. [PubMed]Uehara S, Uno Y, Inoue T, Okamoto E, Sasaki E, and Yamazaki H. Marmoset
cytochrome P450 2J2 mainly expressed in small intestines and livers effectively
metabolizes human P450 2J2 probe substrates, astemizole and terfenadine.
Xenobiotica, 46,977-985,2016. [PubMed]Hosaka S, Murayama N, Satsukawa M, Uehara S, Shimizu M, Iwasaki K, IwanoS, Uno Y, and Yamazaki H. Identification of putative substrates for cynomolgus
monkey cytochrome P450 2C8 by substrate depletion assays with 22 human P450
substrates and inhibitors. Biopharm. Drug Dispos., 37, 310-313, 2016. [PubMed]

Higuchi Y, Kawai K, Kanai T, Yamazaki H, Chesne C, Guguen-Guillouzo C, andSuemizu H. Functional polymer-dependent 3D culture accelerates thedifferentiation of HepaRG cells into mature hepatocytes. Hepatol.Res., 46,10451057, 2016. [PubMed]Utoh M, Suemizu H, Mitsui M, Kawao M, Toda A, Uehara S, Uno Y, Shimizu M,
Sasaki E, and Yamazaki H. Human plasma concentrations of cytochrome P450
probe cocktails extrapolated from pharmacokinetics in mice transplanted withhuman hepatocytes and from pharmacokinetics in common marmosets using
physiologically based pharmacokinetic modeling. Xenobiotica, 46, 1049-1055,2016. [PubMed]

Yonekura H, Murayama N, Yamazaki H, and Sobeu K. A case of delayed
emergence following propofol anesthesia: genetic analysis. Anesth.Analg.,7, 243246, 2016. [PubMed]

Togashi K, Mutaguchi K, Kumuro S, Kataoka M, Yamazaki H, and Yamashita S.
Systematic approach to optimize a pretreatment method for ultrasensitive
LC/MS/MS analysis of multiple target compounds in biological samples.
J.Sep.Sci., 39, 3212-3220, 2016. [Link]

Iwasaki K, Kitsugi Y, Ikeda K, Yoshikawa T, Hosaka S, Uehara S, Uno Y, Utoh
M, and Yamazaki H. In vivo individual variations in pharmacokinetics ofefavirenz in cynomolgus monkeys genotyped for cytochrome P450 2C9. Biopharm.
Drug Dispos., 37, 379-383, 2016. [PubMed]Yamazaki H, Suemizu H, Kazuki Y, Oofusa K, Kuribayashi S, Shimizu M,
Ninomiya S, Horie T, Shibata N, and Guengerich F P. Assessment of protein
binding of 5-hydroxythalidomide bioactivated in humanized mice with human
P450

3A-chromosomeorhepatocytes

bytwo-dimensional

electrophoresis/accelerator mass spectrometry. Chem. Res. Toxicol., 29, 1279-

1281, 2016. [PubMed]
Takahashi T, Ohtsuki Y, Uno Y, Utoh M, Yamazaki H, and Kume T. Preincubation with cyclosporine A potentiates its inhibitory effects on pitavastatin
uptake mediated by recombinantly expressed cynomolgus monkey hepaticorganic anion transporting polypeptide. Biopharm. Drug Dispos., 37, 479-490,
2016. [PubMed]

Mori K, Saito R, Nakamaru Y, Shimizu M, and Yamazaki H. Physiologically
based pharmacokinetic-pharmacodynamic modeling to predict concentrations
and actions of sodium-dependent glucose transporter 2 inhibitor canagliflozin inhuman intestines and renal tubules. Biopharm. Drug Dispos., 37, 491–506, 2016.
[PubMed]Shimada T, Kakimoto K, Takenaka S, Koga N, Uehara S, Murayama N,Yamazaki H, Kim D, Guengerich F P, and Komori M. Roles of human CYP2A6and monkey CYP2A24 and 2A26 cytochrome P450 enzymes in the oxidation of2,5,2',5'-tetrachlorobiphenyl. Drug Metab. Dispos., 44, 1899-1909, 2016.
[PubMed]Uehara S, Kawan, M, Murayama N, Uno Y, Utoh M, Inoue T, Sasaki E, andYamazaki H. Oxidation of R- and S-omeprazole stereoselectively mediated byliver microsomal cytochrome P450 2C19 enzymes from cynomolgus monkeys andcommon marmosets . Biochem. Pharmacol., 120, 56-62, 2016. [PubMed]【総説】Uno Y, Uehara S, and Yamazaki H. Utility of non-human primates in drug
development: comparison of non-human primate and human drug-metabolizing
cytochrome P450 enzymes. Biochem. Pharmacol., 121, 1-7, 2016. [PubMed]Yamazaki H, Suemizu H, Mitsui M, Shimizu M, and Guengerich F P. Combining
Chimeric mice with humanized liver, mass spectrometry, and physiologicallybased pharmacokinetic modeling in toxicology. Chem. Res. Toxicol., 29, 1903-1911,
2016. [PubMed]

Autrup H N, Berry S C L, Cohen S M, Creppy E E, de Camargo J L, Dekant W,Dietrich D, Galli C L, Goodman J I, Gori G B, Greim H A, Klaunig J E, Lotti M,Marquardt H W, Wallace K B, and Yamazaki H. Whither the impending european
regulation of presumed endocrine disruptors? Regul. Toxicol. Pharmacol., 82, A1A2, 2016. [PubMed]Aschner M, Autrup H N, Berry S C, Boobis A R, Cohen S M, Creppy E E, DekantW, Doull J, alli C L, Goodman J I, Gori G B, Greim H A, Joudrier P, Kaminski N
E, Klaassen C D, Klaunig J E, Lotti M, Marquardt H W J, Pelkonen O, Sipes I G,

Wallace K, and Yamazaki H. Upholding science in health, safety andenvironmental risk assessments and regulations. Toxicology, 371, 12-16, 2016.
[PubMed]【著書】
Yamazaki H, Chowdhury G and Guengerich F P. Activation of Thalidomide toReactive Metabolites by Autoinduced Human Cytochrome P450 3A Enzymes,
with Substrate Cooperativity, and Implications for Development of Analogs. In:Advances in Medicine and Biology, Vol. 93, Ed. L.V. Berhardt, pp. 23-30,
Hauppauge, NY, USA: Nova Science Publishers, Inc, 2016.