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Disposition and metabolism of [3H]gliclazide in rats

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Summary

Absorption, distribution, excretion and metabolism of [3H]gliclazide, N-(3-3H-4-methylbenzenesulfonyl)-N′-(3-azabicyclo-[3,3,0]oct-3-yl]urea, a new hypoglycemic agent possessing unique pharmacological properties, were studied by radiometry and autoradiography in rats after oral administration in 10 mg/kg.

Absorption of [3H]gliclazide was found to be complete, since the sum of urinary and biliary radioactivity accounted for total recovery of administered dose. Blood levels reached maximum 1 hr after administration and then biphasically declined with the half lives of about 2 and 5 hrs, respectively. The biphasic decrease of blood levels was partly due to the formation of tritiated water in the blood. Radioactivity was high in the liver, kidney and blood: other tissue levels involving pancreas were lower than blood level with the exception of digestive tracts. Half lives of most tissue radioactivity were within several hours of each other. Most of the radioactivity in the tissues 24hrs after administration was considered to be tritiated water. A moderate level of radioactivity was found in fetal tissues except for brain early after administration. [3H]Gliclazide radioactivity was mostly excreted in urine (about 80% of dose) and partly in feces. Biliary excretion of radioactivity amounted to about 40% of dose. Three major metabolites were found in urine and identified by mass spectrometry, gas chromatography-mass spectrometry and nuclear magnetic resonance. One metabolite was gliclazide hydroxylated at methyl carbon of tolyl group. The other two were isomers of gliclazide hydroxylated at different positions of azabicyclo-octyl ring.

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Authors and Affiliations

  1. Faculty of Nutrition, Kobe-Gakuin University, Japan

    Nanaya Tamaki

  2. Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, 564, Suita, Osaka, Japan

    Hisashi Miyazaki Ph.D., Toshihiko Fujii, Koji Yoshida, Satoshi Arakawa, Hideo Furukawa, Hirosato Suzuki, Akira Kagemoto & Masahisa Hashimoto

Authors
  1. Hisashi Miyazaki Ph.D.
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  2. Toshihiko Fujii
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  3. Koji Yoshida
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  4. Satoshi Arakawa
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  5. Hideo Furukawa
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  6. Hirosato Suzuki
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  7. Akira Kagemoto
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  8. Masahisa Hashimoto
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  9. Nanaya Tamaki
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Miyazaki, H., Fujii, T., Yoshida, K. et al. Disposition and metabolism of [3H]gliclazide in rats. European Journal of Drug Metabolism and Pharmacokinetics 8, 117–131 (1983). https://doi.org/10.1007/BF03188737

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  • DOI: https://doi.org/10.1007/BF03188737

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