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Influence of exposure and infusion times on the cytotoxicity and pharmacokinetics of cis-malonato[(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)

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dc.contributor.authorKim, Hun-Taek-
dc.contributor.authorKim, D.-K.-
dc.contributor.authorCho, Yong-Baik-
dc.contributor.authorKim, Taek-Soo-
dc.contributor.authorJung, I-
dc.contributor.authorKim, Key H.-
dc.contributor.authorHeo, Dae Seog-
dc.contributor.authorBang, Yung-Jue-
dc.contributor.authorShin, Sang-Goo-
dc.contributor.authorKim, Noe Kyeong-
dc.date.accessioned2021-01-31T11:06:08Z-
dc.date.available2021-01-31T11:06:08Z-
dc.date.issued1998-01-
dc.identifier.citationCancer Chemotherapy and Pharmacology, Vol.41 No.2, pp.109-116-
dc.identifier.issn0344-5704-
dc.identifier.other119218-
dc.identifier.urihttps://hdl.handle.net/10371/173024-
dc.description.abstractThe effect of exposure time on the in vitro cytotoxicity of a new platinum complex, cis-malonato-[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II) (SKI 2053R) and cisplatin (CDDP) toward two human lung-adenocarcinoma cell lines (PC-9, PC-14) and two human stomach-adenocarcinoma cell lines (KATO III, MKN-45) was investigated by variation of the exposure time (1, 4, 12, and 24 h) and drug concentration to yield a constant product of drug concentration times exposure time (C x T). Exposure of cancer cells to low concentrations of SKI 2053R for 12 or 24 h resulted in a greater killing effect than did 1- or 4-h exposure to 24- or 6-fold higher concentrations; the inhibitory effects of SKI 2053R on the colony formation of all tumor cell lines except for KATO III were significantly increased with increasing exposure time (P < 0.05), However, the inhibitory effects of CDDP against all tumor cell lines tested except for PC-14 were inversely correlated with increasing exposure time (P < 0.05). The intracellular accumulation of SKI 2053R and CDDP was measured under the same conditions used in the cell-survival assay using MKN-45 cells. The amount of platinum accumulated from SKI 2053R into MKN-45 cells was greater for the treatment involving low concentrations and long-term exposures (12 and 24 h) than for that using high concentrations and short-term exposures (1 and 4 h) at the constant C x T values, however, the increased accumulation of CDDP was more prominent as the concentration was increased, even if the exposure rime became shorter. The pharmacokinetics studies of SKI 2053R following 1-, 4-, 12-, and 24-h infusions were performed in beagle dogs. A single dose of SKI 2053R (5.0 mg/kg) was successively given over various infusion periods to three beagle dogs at 3-week intervals. The peak levels of ultrafiltrable platinum observed for SKI 2053R at the 1-, 4-, 12-, and 24-h infusions were 3.10 +/- 0.49 (mean +/- SD), 1.24 +/- 0.06, 0.43 +/- 0.07, and 0.25 +/- 0.04 mu g/ml, respectively. The mean binding ratios of platinum from SKI 2053R to plasma protein at the end of 1-, 4-, 12-, and 24-h infusions were approximately 91%, 73%, 53%, and 51%, respectively. The steady-state level of free platinum was maintained during long-term infusions (12 and 24 h) after short periods (1-3 h) from the start of the infusion. This study strongly suggests that the therapeutic efficacy of SKI 2053R given by continuous long-term infusion should be investigated in future clinical studies.-
dc.subjectSKI 2053R-
dc.subjectin vitro cytotoxicity-
dc.subjectpharmacokinetics-
dc.titleInfluence of exposure and infusion times on the cytotoxicity and pharmacokinetics of cis-malonato[(4R, 5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)-
dc.typeArticle-
dc.contributor.AlternativeAuthor방영주-
dc.identifier.doi10.1007/s002800050716-
dc.citation.journaltitleCancer Chemotherapy and Pharmacology-
dc.identifier.scopusid2-s2.0-0031882342-
dc.citation.endpage116-
dc.citation.number2-
dc.citation.startpage109-
dc.citation.volume41-
dc.identifier.urlhttps://link.springer.com/article/10.1007/s002800050716-
dc.identifier.rimsid119218-
dc.identifier.sciA1998YK93900004-
dc.contributor.affiliatedAuthorBang, Yung-Jue-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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