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Abstract

Pharmacokinetics, tissue distribution, and excretion of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3- dioxolane]platinum(II) in dogs.

Y B Cho, K H Kim and D K Kim
Drug Metabolism and Disposition November 1995, 23 (11) 1280-1285;
Y B Cho
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K H Kim
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D K Kim
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Abstract

The pharmacokinetics, tissue distribution, and excretion of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3- dioxolane]platinum(II) (SKI 2053R), a new potential anticancer agent, were investigated in dogs after a single intravenous administration of [14C]SKI 2053R (7 mg/kg, 100 microCi/kg). Total radioactivity in the plasma and ultrafiltrable plasma declined in a biexponential fashion with the initial half-lives of 0.63 +/- 0.05 hr (mean +/- SD) and 0.53 +/- 0.05 hr, and with the terminal half-lives of 51.08 +/- 3.26 hr and 15.19 +/- 3.75 hr, respectively. Radioactivity was well distributed into all tissues except the central nervous system. The majority of the radioactivity was found in the gastrointestinal contents, urine, and organs of elimination at all time points. The distribution pattern of [14C]SKI 2053R in the whole-body autoradiograms was consistent with that observed by the measurement of tissue concentrations. The 0-7 days cumulative urinary and fecal recoveries of total radioactivity were 87.30 +/- 2.93% and 8.68 +/- 1.30%, respectively, resulting in a total recovery of 95.98 +/- 1.61% of the administered dose. A large portion of [14C]SKI 2053R was distributed into the cellular fraction of mouse or rat blood, but was not into that of dog or human blood in vitro. The in vitro and in vivo binding of [14C]SKI 2053R to plasma protein was minimal to moderate.

 

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Drug Metabolism and Disposition
Vol. 23, Issue 11
1 Nov 1995
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Abstract

Pharmacokinetics, tissue distribution, and excretion of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3- dioxolane]platinum(II) in dogs.

Y B Cho, K H Kim and D K Kim
Drug Metabolism and Disposition November 1, 1995, 23 (11) 1280-1285;

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Abstract

Pharmacokinetics, tissue distribution, and excretion of cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3- dioxolane]platinum(II) in dogs.

Y B Cho, K H Kim and D K Kim
Drug Metabolism and Disposition November 1, 1995, 23 (11) 1280-1285;
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