PK-PD modeling of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine and the enhanced antitumor effect of its phospholipid derivatives in long-circulating liposomes

Takada, Akitsugu; Kamiya, Hiroyuki; Shuto, Satoshi; Matsuda, Akira; Harashima, Hideyoshi

PK-PD modeling of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine and the enhanced antitumor effect of its phospholipid derivatives in long-circulating liposomes

Takada, Akitsugu; Kamiya, Hiroyuki; Shuto, Satoshi et al.

International Journal of Pharmaceutics, 2009, 377(1-2), 52-59

Permalink : https://hdl.handle.net/2115/38949

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アクセス権	open access
URI	https://hdl.handle.net/2115/38949
タイトル	PK-PD modeling of 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine and the enhanced antitumor effect of its phospholipid derivatives in long-circulating liposomes
著者	Takada, Akitsugu ; Kamiya, Hiroyuki ; Shuto, Satoshi ; Matsuda, Akira ; Harashima, Hideyoshi
著者名 Takada, Akitsugu
著者名 Kamiya, Hiroyuki
著者名 Shuto, Satoshi
e-Rad_Researcher 90157313 著者名 Matsuda, Akira
e-Rad_Researcher 00183567 著者名 Harashima, Hideyoshi
言語	英語
キーワード	3'-ethynylcytidine
	antitumor effect
	PK-PD modeling
	phospholipid derivatives
	liposome
	minimum effective concentration
発行日	2009-07-30
出版者	Elsevier
収録物名	International Journal of Pharmaceutics
巻(号)	377(1-2)
ページ	52-59
抄録	The efficacy of an antitumor nucleoside, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (3'-ethynylcytidine, ECyd), was analyzed in vitro and in vivo. The in vivo antitumor effect of ECyd encapsulated into long-circulating liposomes was also examined. Based on pharmacokinetic (PK) and pharmacodynamic (PD) analyses, a model that quantitatively explains the in vivo effects of ECyd was proposed, using the concept of minimum effective concentration. The model suggests that ECyd followed a time-dependent mechanism of action in vivo, and that availability of ECyd in tumor tissue was highly important. To improve the availability of ECyd, its phospholipid derivatives were synthesized and encapsulated into long-circulating liposomes, which increased the antitumor effect. These results indicate that it is very important to design carriers of antitumor drugs based on PK-PD modeling.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0378-5173
NCID	AA00680771
関連情報	PMID 19426792
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ijpharm.2009.04.039