平成 26 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
薬物動態学 研究室
【原著】

Suemizu H, Sota S, Kuronuma M, Shimizu M, Yamazaki H. Pharmacokinetics and effects on serumcholinesterase activities of organophosphorus pesticides acephate and chlorpyrifos in chimeric micetransplanted with human hepatocytes. Regul.Toxicol.Pharmacol., 70, 468-473,(2014).[PubMed]
Uno Y, Matsushita A, Shukuya M, Matsumoto Y, Murayama N, Yamazaki H. CYP2C19
polymorphisms account for inter-individual variability of drug metabolism in cynomolgus macaques.
Biochem. Pharmacol., 91, 242-248, (2014).[PubMed]
Yamashita M, Suemizu H, Murayama N, Nishiyama S, Shimizu M, Yamazaki H. Human plasma
concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics establishedin in vivo experiments with chimeric mice with humanized liver and physiologically based
pharmacokinetic modeling. Regul.Toxicol.Pharmacol. 70, 214-221, (2014).[PubMed]
Uno Y, Uehara S, Kohara S, Murayama N, Yamazaki H. Polymorphisms of CYP2D17 in cynomolgus
and rhesus macaques: an evidence of the genetic basis for the variability of CYP2D-dependent drug
metabolism. Drug Metab. Dispos., 42, 1407-1410 (2014).[PubMed]
Shimizu M, Iwano S, Uno Y, Uehara S, Inoue T, Murayama N, Onodera J, Sasaki E, Yamazaki H.
Qualitative de novo analysis of full length cDNA and quantitative analysis of gene expression forcommon marmoset (Callithrix jacchus) transcriptomes using parallel long-read technology and shortread sequencing. PLoS One, 9, e100936 (2014).[PubMed]
Yamazaki M, Shimizu M, Uno Y, Yamazaki H. Drug oxygenation activities mediated by livermicrosomal flavin-containing monooxygenases 1 and 3 in humans, monkeys, rats, and minipigs.
Biochem. Pharmacol., 90, :159-165 (2014).[PubMed]
Ozasa H, Shimizu M, Koizumi A, Wakabayashi A, Yamazaki H. Trimethylamine generation inpatients receiving hemodialysis treated with l-carnitine. Clin.Kidney J., 7, 329 (2014).[Extract]
Nakamaru Y, Hayashi Y, Sekine M, Kinoshita S, Thompson J, Kawaguchi A, Davies M, Jurgen
Heuer H, Yamazaki H, Akimoto K. Effect of ketoconazole on the pharmacokinetics of the dipeptidyl
peptidase-4 Inhibitor teneligliptin: an open-label study in healthy white subjects in Germany.
Clin.Ther, 36, 760-769 (2014).[PubMed]

Higashi E, Ando A, Iwano S, Murayama N, Yamazaki H, Miyamoto S. Hepatic microsomal UDPglucuronosyltransferase (UGT) activities in the microminipig. Biopharm. Drug Dispos., 35, 313-320(2014).[PubMed]
Koyanagi T, Yamaura K, Yano K, Kim S, Yamazaki H. Age-related pharmacokinetic changes ofacetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys
and beagle dogs. Xenobiotica, 44, 893-901 (2014).[PubMed]
Uehara S, Murayama N, Nakanishi Y, Nakamura C, Hashizume T, Zelden D C, Yamazaki H, Uno Y.
Immunochemical detection of cytochrome P450 enzymes in small intestine microsomes of male andfemale untreated juvenile cynomolgus monkeys. Xenobiotica, 44, 769-774 (2014).[PubMed]
Yajima K, Uno Y, Murayama N, Uehara S, Shimizu M, Nakamura C, Iwasaki K, Utoh M, Yamazaki,
H. Evaluation of 23 lots of commercially available cryopreserved hepatocytes for induction assays ofhuman cytochromes P450. Drug Metab. Dispos, 42, 867-871 (2014). [PubMed]
Murayama N, van Beuningen R, Suemizu H, Guguen-Guillouzo C, Shibata N, Yajima K, Utoh M,Shimizu M, Chesne C, Nakamura M, Guengerich F P, Houtman R, Yamazaki H. Thalidomide
increases human hepatic cytochrome P450 3A enzymes by direct activation of pregnane X receptor.,
Chem.Res.Toxicol., 27，304-307 (2014). [PubMed]
Zonios D, Yamazaki H, Murayama N, Natrarajan V, Palmore T, Childs R, Skinner J, Bennett J.
Voriconazole metabolism, toxicity and the effect of cytochrome P450 2C19 genotype. J.Infect.Dis.,
209, 1941-1948 (2014). [PubMed]
Niwa T, Yasumura M, Murayama N and Yamazaki H. Comparison of catalytic properties ofcytochromes P450 3A4 and 3A5 by molecular docking simulation. Drug Metab.Lett. 8 ，43-50(2014).[PubMed]
Shimizu M, Allerston C K, Shephard E A, Yamazaki H, Phillips I. R. Relationships between flavincontaining monooxygenase 3 (FMO3) genotype and trimethylaminuria phenotype in a Japanese
population, Brit.J. Clin. Pharmacol., 77, 839-851 (2014).[PubMed]Nakamaru Y, Hayashi Y, Ikegawa R, Kinoshita S, Madera B P, Gunput D, Kawaguchi A, Davies M,Mair S, Yamazaki H, Kume T, Suzuki M. Metabolism and disposition of the dipeptidyl peptidase IV
inhibitor teneligliptin in humans. Xenobiotica、44, 242-253 (2014).[PubMed]
Higuchi, Y., Kawai, K., Yamazaki, H., Nakamura, M., Bree, F., Guillouzo, C., and Suemizu, H. The
human hepatic cell line HepaRG cells, possible cell source for steady generation of humanized liver
TK-NOG mice. Xenobiotica, 44, 146-153 (2014).[PubMed]Ohyama, K., Murayama, N., Shimizu, M., and Yamazaki, H. Drug interactions of diclofenac and its
oxidative metabolite with human liver microsomal cytochrome P450 1A2-dependent drug oxidation.
Xenobiotica, 44, 10-16 (2014).[PubMed]
Chowdhury G, Shibata N, Yamazaki H, Guengerich FP. Human cytochrome P450 oxidation of 5hydroxythalidomide and pomalidomide, an amino analog of thalidomide. Chem. Res.Toxicol., 27,147-156 (2014).[PubMed]【著書】
山崎浩史，「薬物動態学第二版」、栄田敏之、山崎浩史, 灘井雅行 編著、廣川書店、東京、2014.
Yamazaki H, Fifty Years of Cytochrome P450 Research, (ed.) Yamazaki H, Springer, Tokyo, 2014. [link]【総説】
Yamazaki H. Drug-induced liver toxicity studies: research into human metabolites clarifies their role in drugdevelopment. Drug Metab.Pharmacokinet., 29, 111, 2014.[PubMed]
Niwa T, Inagawa Y, Yamazaki H. Drug interactions between nine antifungal agents and drugs metabolized by human
cytochromes P450. Curr.Drug Metab., 15, 651-678, 2014. [PubMed]【依頼・招待講演等】
山崎浩史、医療薬学フォーラム 2014／第 22 回クリニカルファーマシーシンポジウム「レボカルニチンを使う透析患者さんの体臭を科学する－個の医療－」、2014 年 6 月、東京
山崎浩史、第 41 回日本毒性学会年会「医薬品開発におけるヒト代謝物研究の役割」、2014 年 7 月、神戸
Yamazaki H, 19th North American ISSX/ 29th JSSX Annual Meeting, October, 2014, San Francisco, ”Reactive
metabolite formation of drugs by human P450s in chimeric mice with humanized liver”. 2014 年 10 月
Yamazaki H, 19th North American ISSX/ 29th JSSX Annual Meeting, October, 2014, San Francisco, ”Metabolic
activation and fate of xenobiotics determined by polymorphic drug-metabolizing enzymes”. 2014 年 10 月