Document Detail

Pharmacokinetics and antitumor activity of a new platinum compound, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3- dioxolane]platinum(II), as determined by ex vivo pharmacodynamics.
MedLine Citation:
PMID:  7497577     Owner:  NLM     Status:  MEDLINE    
The pharmacokinetics and ex vivo pharmacodynamics studies on cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3- dioxolane]platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP), and carboplatin (CBDCA) were performed in beagle dogs. Equitoxic doses of SKI 2053R, CDDP, and CBDCA (7.5, 2.5, and 15.0 mg/kg, respectively) were given by i.v. bolus to three beagle dogs in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the three drugs declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0-->infinity) determined for ultrafiltrable platinum derived from SKI 2053R, as an active component, was 7.72 +/- 2.74 micrograms h ml-1 (mean +/- SD), with an initial half-life of 0.37 +/- 0.20 h, a terminal half-life of 2.19 +/- 0.93 h, a total clearance of 16.83 +/- 4.76 ml min-1 kg-1, and a steady-state volume of distribution of 1.57 +/- 0.30 l/kg. The ex vivo antitumor activity of SKI 2053R was assessed using the ultrafiltrable plasma against two human lung-adenocarcinoma cell lines (PC-9 and PC-14) and five stomach-adenocarcinoma cell lines (MKN-45, KATO III, SNU-1, SNU-5, and SNU-16) by tetrazolium-dye (MTT) assay and was compared with that of CDDP and CBDCA using an antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value was shown to be ranked in the following order: SKI 2053R > CBDCA > CDDP. The mean ATI values recorded for SKI 2053R and CBDCA were significantly (P < 0.05) higher than that noted for CDDP; however, no statistically significant difference was observed between SKI 2053R and CBDCA, suggesting that the antitumor activity of SKI 2053R is superior to that of CDDP and is equivalent to that of CBDCA. These results suggest that SKI 2053R is a promising candidate for further development as a clinically useful anticancer drug.
D K Kim; H T Kim; J H Tai; Y B Cho; T S Kim; K H Kim; J G Park; W S Hong
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  37     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  1995  
Date Detail:
Created Date:  1996-01-17     Completed Date:  1996-01-17     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Life Science Research Center, Sunkyong Industries, Kyungki-Do, Korea.
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MeSH Terms
Antineoplastic Agents / pharmacokinetics*,  pharmacology
Carboplatin / pharmacokinetics
Cisplatin / pharmacokinetics
Malonates / pharmacokinetics*,  pharmacology
Organometallic Compounds / pharmacokinetics*,  pharmacology
Organoplatinum Compounds*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Malonates; 0/Organometallic Compounds; 0/Organoplatinum Compounds; 146665-77-2/SKI 2053R; 15663-27-1/Cisplatin; 41575-94-4/Carboplatin

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