SPECIES DIFFERENCES IN EXCRETION PATTERN AND TOXICITY OF SULBENICILLIN
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概要
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The results of toxicity studies on sulbenicillin (SB-PC) in rats, dogs and monkeys as well as distribution and excretion patterns in these animals and humans were reviewed and, taking into account the results of its clinical trials in 6376 patients, the following conclusion was obtained. 1. There was marked species difference in excretion and distribution of SB-PC. In dogs, unlike other animals including humans, excretion of SB-PC into bile was larger than that into urine, and its distribution in the liver at an extraordinarily high concentration was observed. When SB-PC was intravenously injected to dogs at various dosages, transient but dose-related hepatotoxic signs appeared, and a few animals died at 1500 mg/kg/day. 2. There were no abnormalities in rats treated intramuscularly with 2500 mg/kg/day of SB-PC for 6 months except for a local irritation at the injection site. The excretion pattern of SB-PC in cynomolgus monkeys was quite similar to that in humans, and they tolerated daily intravenous injections at 1500 mg/kg/day for one month well. None of the animals showed any significant changes in hematological, biochemical and histological examinations. 3. In clinical trials of SB-PC, intravenous infusion at 30 g (15 gx 2)/day/man did not affect the normal function of the liver and kidneys in the patients. The above results were compared with those reported for carbenicillin (CB-PC) and it was indicated that SB-PC is less toxic than CB-PC in humans.
- 日本トキシコロジー学会の論文
- 1976-07-15
著者
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Nomura Masaji
Central Research Division Takeda Chemical Industries Ltd.
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Kanabayashi Teruhiko
Central Research Division Takeda Chemical Industries Ltd.
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TAKANO Kiichi
Central Research Division, Takeda Chemical Industries, Ltd.
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YOKOTANI Hajime
Central Research Division, Takeda Chemical Industries, Ltd.
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MURATA Yukio
Central Research Division, Takeda Chemical Industries, Ltd.
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AONO Minamoto
Central Research Division, Takeda Chemical Industries, Ltd.
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Aono Minamoto
Central Research Division Takeda Chemical Industries Ltd.
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Aono Minamoto
Central Reaearch Division Takeda Chemical Industries Ltd.
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Takano Kiichi
Central Research Division Takeda Chemical Industries Ltd.
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Yokotani Hajime
Central Research Division Takeda Chemical Industries Ltd.
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Murata Yukio
Central Research Division Takeda Chemical Industries Ltd.
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