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Res Commun Mol Pathol Pharmacol. 1995 Dec;90(3):347-62.

Stability, tissue metabolism, tissue distribution, and blood partition of DA-1131, a new carbapenem.

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1
College of Pharmacy, Seoul National University, Korea.

Abstract

The stability of DA-1131 after incubation in various pH solutions, human plasma, human urine, human gastric juice, rat liver homogenates and rat whole blood, the disappearance of DA-1131 after incubation in the 9000g supernatant fraction of various rat tissue homogenates in the presence of NADPH, the tissue distribution of DA-1131 after intravenous (i.v.) administration of DA-1131, 50 mg/kg, to rats, and the blood partition of DA-1131 between plasma and blood cells from rabbit blood were studied. DA-1131 was unstable when incubated in various pH solutions, especially at low and high pHs at the DA-1131 concentration of 10 micro g/ml; the degradation half-lives of DA-1131 were 0.260, 1.23, 2.20, 7.16, 14.2, 10.5, 31.3, 21.3, 0.262, 0.241, and 1.45 hr for pH solutions of 1-11, respectively. DA-1131 was also unstable after incubation in human plasma, rat liver homogenates, and human gastric juice. However, DA-1131 seemed to be sable in human plasma for up to 12 hr storage at -20 degrees C. The spleen, kidney, liver, lung, mesentery, and stomach homogenates from rats showed metabolic activity to DA-1131. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The tissue-to-plasma ratios of DA-1131 were lower than unity in all tissues studied except kidney when each tissue was collected at 30 min after i.v. administration of DA-1131 to rats. The plasma-to-blood cell concentration ratios of DA-1131 were independent of DA-1131 blood concentrations when the whole blood was incubated up to 120 min; the mean values were 5.56 +/- 1.47, 5.80 +/- 2.19, and 4.61 +/- 1.82 at DA-1131 blood concentrations of 2, 10, and 20 microgram/ml, respectively, rabbits A-C. There was also considerable in vivo and in vitro blood storage effect in the plasma concentration of DA-1131 in rabbits.

PMID:
8746482
[Indexed for MEDLINE]

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