株式会社三菱ケミカルホールデイングス

田辺三菱製薬株式会社

研究本部 薬物動態研究所

筬島 智則（Osajima Tomonori）

研究業績目録

【学会発表】① 日本薬剤学会第14年会（1999年3月26日～1999年3月28日）（Oral）

演題：生体内分解性高分子を用いた難水溶性抗精神病薬の徐放性注射剤の開発

演者：○ 筬島 智則、園田 直子、木野 繁美、山田 一磨呂、水田 博彰、有馬 徳行

② 第16回日本Drug Delivery System（DDS）学会（2000年7月28日～2000年7月29日）（Poster）演題：生体内分解性高分子を用いた難水溶性抗精神病薬の徐放性注射剤の開発

－ブロムペリドールマイクロスフェアのin vivo評価－

演者：○ 筬島 智則、稲葉 賢一、岩久 義範、山田 一磨呂、有馬 徳行

③ 67th ACR/ARHP Annual Scientific Meeting （23/10/2003 －30/10/2003）（Poster）演題：Pharmacokinetics and Pharmacodynamics of Y-700, A Potent and Non-Renal

Excretion Type of Xanthine Oxidase Inhibitor, in Healthy Male Volunteers演者：○ Tomonori Osajima, Miho Kamezawa, Atsushi Fukunari, Hiroyuki Mori, Junichi

Iwane, Ichimaro Yamada.

④ Annual European Congress of Rheumatology, EULAR 2003（18/6/2003－21/6 2003 ）（Poster）演題：SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF Y-700,

A NON-RENAL EXCRETION TYPE XANTHINE OXIDASE INHIBITOR, IN HEALTHY VOLUNTEERS

演者：○ S. Noma, M. Verho, J. Iwane, P. Rolan, I. Yamada, T. Osajima, M. Kamezawa

⑤ 第18回日本薬物動態学会年会 （2003年10月8日～2003年10月10日）（Poster）演題：新規キサンチンオキシダーゼ（XO）阻害薬Y-700のラットおよびイヌにおける体内動態

演者：○ 亀澤 美穂、筬島 智則、舩越 拓志、山田 一磨呂、魚浜 克巳、 三次 孝一

⑥ 2nd World Congress of the Board of Pharmaceutical Sciences of FIP （30/5/2004－3/6/2004）

（Poster）演題：PK/PD study of Y-700, a novel xanthine oxidase inhibitor, in healthy male volunteers演者：○ Tomonori Osajima, Miho Kamezawa, Shunya Noma, Ruriko Ikegawa, Junichi Iwane,

Ichimaro Yamada

⑦ 13th NA ISSX-20th JSSX Joint Meeting（23/10/2005－27/10/2005）（Poster）演題：CARRIER-MEDIATED HEPATIC UPTAKE OF A NEW NON-RENAL EXCRETION

TYPE URIC ACID GENERATION INHIBITOR, Y-700演者：○ K. Nakamura, Y. Sai, Y. Kato, I. Tamai, T. Osajima, M. Kamezawa,

I. Yamada and A. Tsuji（金沢大学 薬学部と共同研究）

⑧ International Stroke Conference 2007（7/2/2007－9/2/2007）（Poster）演題： Effect of Edaravone, a Neuroprotectant Approved in Japan for Indications of

Acute Ischemic Stroke, in Rodent and Primate演者：○ Satoshi Yuki, Toshiaki Akira, Hiroko Kondou, Tomonori Osajima,

Takashi Tashiro, Kaneyoshi Honjo

【論文】

① 雑誌：Nucleosides Nucleotides Nucleic Acids. 2004 Oct;23(8-9):1123-5表題：Pharmacokinetics/pharmacodynamics of Y-700, a novel xanthine oxidase inhibitor,

in rats and man.著者：Yamada I, Fukunari A, Osajima T, Kamezawa M, Mori H, Iwane J.

② 雑誌： 痛風と核酸代謝．28(1), 37, 2004-07-01

表題 ：新規キサンチンオキシダーゼ阻害薬Y-700のPharmacokinetics/Pharmacodynamics

（PK/PD）と人種差について

著者：山田一磨呂, 筬島智則, 亀澤美穂, 岩根順一, 池川瑠璃子, 福成篤, 山中寿

③ 雑誌：薬剤学：生命とくすり(0372-7629)63巻Suppl. Page197(2003.03)

表題：非腎排泄型尿酸生合成阻害剤Y-700の肝取り込み機構の解明

著者：中村桂子，崔吉道, 加藤将夫, 玉井郁巳, 筬島智則, 亀澤美穂, 山田一磨呂, 辻彰

（金沢大学 薬学部と共同研究）

2012年4月

APPENDIX

Orange County Convention Center（OCCC）9800 International Drive, Orlando，FL，USMain Number: (407) 685-9800 Toll Free: (800) 345-9845 Email: Info@occc.netWebsite: www.occc.net

＜67th ACR/ARHP Annual Scientific Meeting＞

Pharmacokinetics and Pharmacodynamics of Y-700, A Potent and Non-Renal Excretion Type of Xanthine Oxidase Inhibitor, in Healthy Male Volunteers

Tomonori Osajima1, Miho Kamezawa1, Atsushi Fukunari2, Hiroyuki Mori3, Junichi Iwane4, Ichimaro Yamada1

1 Pharmacokinetics Laboratory, Research Division, Mitsubishi Pharma Corporation2 Discovery Technology Laboratory, Research Division, Mitsubishi Pharma Corporation3 Clinical Pharmacology Department, Development Division, Mitsubishi Pharma Corporation4 International Clinical Research Department, Development Division, Mitsubishi Pharma Corporation

AbstractY-700, 1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid, is currently under development

as a novel xanthine oxidase inhibitor, which is a non-purine selective type drug for treating patients with gout and hyperuricemia. The objective of this study is to assess pharmacokinetics and pharmacodynamics of Y-700 after singleoral administration of Y-700 to Japanese healthy male volunteers. The obtained findings are shown as follows, 1. Y-700 was rapidly absorbed in reaching Cmax (observed maximum plasma concentration ) in 1.4 to 3.1 hr and eliminated from plasma with long half-life ranging from 23.5 to 40.2 hr. The slopes of regression line between Doseand Cmax or AUC0-∞ (area under the plasma concentration-time curve from time zero to infinity) in the range of

0.5 to 80 mg were 1.107(90% confidential interval(CI) : 1.071 to 1.143) and 1.025(90%CI : 0981 to 1.069), respectively. 2. Y-700 presented mainly in plasma and urinary excretion of Y-700 was only less than 1.5%. The main metabolitein urine was Y-700 glucuronide, and urinary excretion of that was 25.9% of the administrated dose. 3. CLR(renal clearance) showed very small value in comparision with CL/F(apparent oral clearance)and approximately constant value over the dose range investigated. Furthermore, no relationship wasobserved between CLR and Cmax and AUC0-∞.

4. Uric acid concentration and its Δ value(Change from pre-dose value in uric acid concentration in serum ) in

serum decreased dose-dependently.

5. Amount of urinary excretion of uric acid showed dose dependency decrease and that of xanthine and

hypoxanthine showed dose dependency increase. No obvious difference was observed in CLua (fractional uric

acid clearance) between placebo and the dose investigated .

6. It was judged that the pharmacokinetics of Y-700 was not influenced by food. Furthermore, no significant

difference was observed in the excretion amounts of uric acid in urine, and uric acid clearance. However, the

only the excretion amounts of hypoxanthine in urine on Day 1 were significantly lower in the postprandial

administration group than the group dosed under fasting conditions.

Y-700 was demonstrated to be a potent and non-renal excretion type of xanthine oxidase inhibitor in man.

It is thus expected that unlike allopurinol, Y-700 can provide stable and safe control of uric acid levels, even

in patients with renal failure.

Address for correspondence ：Tomonori Osajima, Pharmacokinetics Laboratory, Research Division, Mitsubishi Pharma Corporation, 1-1-1 Kazusakamatari, Kisarazu, Chiba 292-0818, Japan.TEL： +81- 438-52-3549FAX ： +81-438-52-3543 E-mail: Osajima.Tomonori@mg.m-pharma.co.jp

Poster Session ：筬島 智則（左端）

67th ACR/ARHP Annual Scientific Meeting （23/10/2003 －30/10/2003）Orange County Convention Center, Orlando, FL, US