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Pharmacokinetics, stability, and blood partition of 7-anilino-5,8-isoquinolinedione, a new isoquinonlinedione derivative
- Pharmacokinetics, stability, and blood partition of 7-anilino-5,8-isoquinolinedione, a new isoquinonlinedione derivative
- Kim, SH; Moon, YJ; Ryu, CK; Lee, MG
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY
- vol. 107, no. 5-6, pp. 419 - 429
- P J D PUBLICATIONS LTD
- Pharmacokinetics of IQO4, a new isoquinolinedione derivative, after 30-min intravenous administration of the drug, 5 mg/kg, to rats, the stability, and the blood partition between plasma and blood cells of IQO4 were evaluated. After intravenous administration, IQO4 was eliminated fast with the mean total body clearance of 105 ml/min/kg. IQO4 was almost completely metabolized in rats; 5.18% of intravenous dose of IQO4 was excreted in 24-hr urine and IQO4 was under detection limit in whole gastrointestinal tract as 24 hr. IQO4 has a good affinity to liver, small intestine, heart lung, and kidney as reflected to greater-than-unity tissue-to-plasma ratios. IQO4 was unstable in rat whole blood, plasma, and liver homogenates when incubated in a water-bath shaker for 24 hr kept at 37 degrees C and at a rate of 50 oscillations per min. The disappearance rate constants of IQO4 were 0.0611, 0.0436, and 0.174 hr(-1) for rat whole blood, plasma, and liver homogenates, respectively. However, IQO4 was stable for up to 3-hr incubation in human gastric juices. The plasma-to-blood cell concentration ratios of IQO4 were independent of initial blood concentrations of IQO4, 0.5, 2, and 10 mug/ml, when the rabbit whole blood was incubated for up to 120 min; the ratios were in the range of 1.56-3.60. Since IQO4 was unstable in blood, considerable in vitro 'blood storage effect' in the plasma concentration of IQO4 was observed.
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