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

MASAYUKI NADAI, TATAAKI HASEGAWA, KATSUYOSHI KATO, LI WANG, Toshitaka Nabeshima, NOBUO KATO

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)971-974
Number of pages4
JournalJournal of Pharmacy and Pharmacology
Volume45
Issue number11
DOIs
Publication statusPublished - 01-01-1993
Externally publishedYes

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Tobramycin
Lipopolysaccharides
Pharmacokinetics
Glomerular Filtration Rate
Inulin
Extracellular Fluid
Klebsiella pneumoniae
Aminoglycosides
Pharmaceutical Preparations
Half-Life
Kidney

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

NADAI, MASAYUKI ; HASEGAWA, TATAAKI ; KATO, KATSUYOSHI ; WANG, LI ; Nabeshima, Toshitaka ; KATO, NOBUO. / Influence of a Bacterial Lipopolysaccharide on the Pharmacokinetics of Tobramycin in Rats. In: Journal of Pharmacy and Pharmacology. 1993 ; Vol. 45, No. 11. pp. 971-974.
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Influence of a Bacterial Lipopolysaccharide on the Pharmacokinetics of Tobramycin in Rats. / NADAI, MASAYUKI; HASEGAWA, TATAAKI; KATO, KATSUYOSHI; WANG, LI; Nabeshima, Toshitaka; KATO, NOBUO.

In: Journal of Pharmacy and Pharmacology, Vol. 45, No. 11, 01.01.1993, p. 971-974.

Research output: Contribution to journalArticle

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AU - NADAI, MASAYUKI

AU - HASEGAWA, TATAAKI

AU - KATO, KATSUYOSHI

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N2 - 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

AB - 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

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