Bioscience and Microflora
Online ISSN : 1349-8355
Print ISSN : 1342-1441
ISSN-L : 1342-1441
Induction of Lethal Endogenous Escherichia coli Infection in Mice by Administration of 5-FU in Combination with 1-β-D-Arabinofuranosyuracil (Sorivudine)
Koji NOMOTOTeruo YOKOKURANaohiro TOMITA
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1998 年 17 巻 2 号 p. 115-123

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Sorivudine (1-β-D-arabinofuranosyl-5-(E-2-bromovinyl) uracil) is a potent and selective antiviral agent against herpes simplex virus type 1 and varicella-zoster virus. Severe side effects (bone marrow suppression), however, occurred when sorivudine was co-administered with fluorouracil (5-FU)-related anticancer drugs. We have examized the mechanism of the lethal toxicity exerted by the combination treatment. The administration of sorivudine or its major metabolite, 5-(E-2-bromovinyl) uracil (BVU), 1 hr previous to the administration of 5-FU in mice increased the plasma half-life of 5-FU and its area under the curve dramatically. The combination of sorivudine (100 mg/kg) or BVU (20 mg/kg) with sublethal doses of 5-FU (not more than 160 mg/kg) or tegafur (500 mg/kg) induced a lethal endogenous infection of Escherichia coli in all the mice treated, while a single dose of sorivudine, BVU, 5-FU or tegafur did not cause any infection. Streptomycin sulfate protected mice from the lethal toxicity of the drug combinations, suggesting that the toxicity is due to bacterial infection. A parenteral administration of a heat-killed preparation of Lactobacillus casei YIT 9018 (LC 9018) effectively prevented the lethal endogenous infection and escalated the recovery from the chemotherapyinduced hematopoietic injury, suggesting that nonspecific immunopotentiation is also important in preventing the severe side effects of sorivudine in combination with 5-FU-related anticancer drugs.

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