JaLCDOI 10.18926/AMO/31635
フルテキストURL fulltext.pdf
著者 Yamamoto, Junko| Miyagi, Yasunari| Kawanishi, Kunihiro| Yamada, Shinako| Miyagi, Yuji| Kodama, Junichi| Yoshinouchi, Mitsuo| Kudo, Takafumi|
抄録 <p>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 &#60; 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 &#60; 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 &#60; 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.</p>
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
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 10561728
Web of Science KeyUT 000083427100001