Influence of a Bacterial Lipopolysaccharide on the Pharmacokinetics of Tobramycin in Rats

MASAYUKI NADAI, TATAAKI HASEGAWA, KATSUYOSHI KATO, LI WANG, TOSHITAKA NABESHIMA, NOBUO KATO

研究成果: ジャーナルへの寄稿学術論文査読

13 被引用数 (Scopus)

抄録

Abstract— The effects of Klebsiella pneumoniae O3 lipopolysaccharide on the renal handling and distribution characteristics of the aminoglycoside tobramycin were investigated in rats. Tobramycin (2 mg kg−1) and inulin (100 mg kg−1) were administered intravenously 2 h after administration of 50,250 or 500 μg kg−1 lipopolysaccharide. Lipopolysaccharide delayed the disappearance of tobramycin from plasma in a dose‐dependent manner. A dose‐dependent decrease in systemic clearance of tobramycin was observed, although the elimination rate constant and fraction of urinary recovery of unchanged drug were not significantly different in any group. Lipopolysaccharide significantly decreased the central compartment volume of distribution of tobramycin, but did not influence the steady‐state volume of distribution. A dose‐related increase in the ratio of the rate constant of transfer to the peripheral compartment to the rate constant of transfer from peripheral compartment to central compartment was observed. The glomerular filtration rate was significantly decreased by pretreatment with 250 μg kg−1 lipopolysaccharide and the clearance ratio was decreased by 20%, indicating that lipopolysaccharide increases the tubular reabsorption of tobramycin. Our findings suggest that K. pneumoniae O3 lipopolysaccharide modifies the glomerular filtration rate and tubular reabsorption without change in the terminal half‐life and that drug distribution characteristics from the rapidly‐distributing compartment to the peripheral compartment were altered without expansion of the extracellular fluid volume. 1993 Royal Pharmaceutical Society of Great Britain

本文言語英語
ページ(範囲)971-974
ページ数4
ジャーナルJournal of Pharmacy and Pharmacology
45
11
DOI
出版ステータス出版済み - 11-1993
外部発表はい

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学

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