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ID 31635
JaLCDOI
フルテキストURL
著者
Yamamoto, Junko Okayama University
Miyagi, Yasunari Okayama University
Kawanishi, Kunihiro Okayama University
Yamada, Shinako Okayama University
Miyagi, Yuji Okayama University
Kodama, Junichi Okayama University
Yoshinouchi, Mitsuo Okayama University
Kudo, Takafumi Okayama University
抄録

The pharmacodynamic effects of cisdiamminedichloroplatinum(II) (CDDP) in vitro have been reported, but the dosage and exposure time in vitro have not been based on clinical observations of the drug's actions in vivo. In this study, the authors attempted to evaluate the pharmacodynamic effects of CDDP in vitro in terms of cell survival and DNA crosslinking by simulating unbound CDDP administration at varying concentrations to a rat mammary adenocarcinoma line (known as line 66). CDDP exposure was conducted by both constant concentration procedures and a simulated in vivo procedure. Colony formation assay for the surviving fraction and alkaline elution assay for DNA crosslink measurement were performed in order to evaluate the pharmacodynamics of CDDP. Cell survival was a function of the area under the drug concentration time curve (AUC) of unbound CDDP (R2 = 0.77, P < 0.002) for all drug exposure procedures as analyzed by the analysis of covariance test. There was a strong correlation between the surviving fraction and the crosslink index of the total amount of DNA crosslinks (R2 = 0.85, P < 0.0005). Both the total amount of DNA-DNA crosslinks and the DNA-protein crosslinks, of which the latter were dominant, were affected not by the exposure procedures, but by the AUC value (P < 0.002). The thresholds of cytocidal effect were 1.59 mg.h/l for the AUC and 0.008 for the crosslink index. The pharmacodynamic effects in vitro by simulated in vivo exposure were identical to those of constant.

キーワード
pharmacodynamics
pharmacokinetics
simulation
cisplatin
crosslink
Amo Type
Article
発行日
1999-10
出版物タイトル
Acta Medica Okayama
53巻
5号
出版者
Okayama University Medical School
開始ページ
201
終了ページ
208
ISSN
0386-300X
NCID
AA00508441
資料タイプ
学術雑誌論文
言語
English
論文のバージョン
publisher
査読
有り
PubMed ID
Web of Sience KeyUT