新規フルオロキノロン系抗菌薬balofloxacinの生体内動態-マウスおよびイヌにおける^<14>Cbalofloxacinの吸収および排泄-  [in Japanese] Disposition of balofloxacin: Absorption and excretion after single administration of ^<14>C-balofloxacin in mice and dogs  [in Japanese]

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Author(s)

    • 石谷 雅樹 ISHIGAI Masaki
    • 中外製薬株式会社薬物動態研究所 Drug Metabolism and Pharmacokinetics Research Laboratory, Chugai Pharmaceutical Co., Ltd.
    • 中川 俊人 NAKAGAWA Toshito
    • 中外製薬株式会社薬物動態研究所 Drug Metabolism and Pharmacokinetics Research Laboratory, Chugai Pharmaceutical Co., Ltd.
    • 奥富 常雄 OKUTOMI Tsuneo
    • 中外製薬株式会社薬物動態研究所 Drug Metabolism and Pharmacokinetics Research Laboratory, Chugai Pharmaceutical Co., Ltd.
    • 大久保 一三 OHKUBO Kazumi
    • 中外製薬株式会社薬物動態研究所 Drug Metabolism and Pharmacokinetics Research Laboratory, Chugai Pharmaceutical Co., Ltd.
    • 岡崎 彬 OKAZAKI Akira
    • 中外製薬株式会社薬物動態研究所 Drug Metabolism and Pharmacokinetics Research Laboratory, Chugai Pharmaceutical Co., Ltd.

Abstract

新規フルオロキノロン系抗菌薬balofloxacin (BLFX) のマウスおよびイヌにおける吸収および排泄について14C標識したBLFXを用いて検討した。<BR>1. <SUP>14</SUP>C-BLFX経口投与後, 放射能は速やかに吸収された。消失半減期はイヌで比較的長く, イヌの単位投与量当たりのAUC (AUC/dose) は, マウスに比べ20倍以上高い値を示し, 14CBLFX経口投与後の放射能の動態、に動物種間で差異が認められた。<BR>2.尿中にはいずれの動物においてもBLFXとしての排泄量が最も多く, その他BLFXglucuronide (BLFX glu,) およびN-desmethyl BLFXが認められた。一方, 胆汁中あるいは糞中代謝物はイヌではBLFX glu.が最も多かったが, マウスでは未知代謝物が多く認められた。<BR>3.いずれの動物においても<SUP>14</SUP>C-BLFX経口投与後, 投与放射能の大部分が尿中および糞中へ排泄された。また, 静脈内投与後の放射能の排泄は, マウスでは糞中が多くイヌでは尿中および糞中でほぼ同程度であり, 動物種間で放射能の排泄経路が異なることが明らかとなった。

The absorption and excretion of <SUP>14</SUP>C-labeled balofloxacin (BLFX)[±-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methyl-aminopiperidine-1-yl)-4-oxoquinoline-3-carboxylic acid], a new fluoroquinolone antimicrobial agent, was studied in mice and dogs.<BR>1. <SUP>14</SUP>C-BLFX was absorbed rapidly after an oral administration in mice and dogs. However, there were species differences in the disposition of radioactivity after <SUP>14</SUP>C-BLFX administration. The elimination halflife in plasma was shorter in dogs than in mice, and the ratio of AUC for dose (AUC/dose) in dogs was greater (>20 times) than that in mice.<BR>2. A large portion of the urinary excretion was unchanged BLFX in mice and dogs, and small amounts of BLFX glucuronide (BLFX glu.) and N-desmethyl-BLFX were found as metabolites. On the other hand, a large portion of the biliary or fecal excretion was BLFX glu. in dogs, and large amounts of unknown metabolites in addition to BLFX glu. were found in mice.<BR>3. After an oral administration of <SUP>14</SUP>C-BLFX, almost all administered radioactivity was excreted into the urine and feces in mice and dogs. Species differences were observed in the excretion routes of radioactivity after an intravenous administration of <SUP>14</SUP>C-BLFX; the urinary excretion rate in dogs was similar to the fecal excretion rate, however, the urinary excretion rate in mice was much lower than the ecal excretion rate.

Journal

  • Japanese Journal of Chemotherapy

    Japanese Journal of Chemotherapy 43, 94-99, 1995-11-27

    Japanese Society of Chemotherapy

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Cited by:  4

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