Effect of a bacterial lipopolysaccharide on biliary excretion of a β- lactam antibiotic, cefoperazone, in rats

S. Haghgoo, T. Hasegawa, M. Nadai, L. Wang, Toshitaka Nabeshima, N. Kato

Research output: Contribution to journalArticle

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Abstract

Klebsiella pneumoniae O3 lipopolysaccharide (LPS) has been found to dramatically modify the pharmacokinetics of the β-lactam antibiotic cefazolin in rats. This study investigated the effect of LPS on the biliary excretion of the β-lactam antibiotic cefoperazone (CPZ) in rats. CPZ is known to he actively secreted into the bile by a carrier-mediated transport system. LPS (250 μg/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CPZ (20 mg/kg). The pharmacokinetic parameters of CPZ were estimated by a noncompartment model. LPS induced a significant decrease in the systemic clearance (by approximately 50%) and an increase in the mean residence time of CPZ. Significant decreases were also seen in the bile flow rate and in the biliary recovery of unchanged CPZ in the LPS-treated rats. LPS tended to increase the proportion of urinary excretion of CPZ. LPS significantly decreased the biliary clearance (by approximately 55%) and renal clearance (by approximately 35%) of CPZ. However, no changes in the volume of distribution at steady state for CPZ were observed between the treatment groups. Our findings suggest that LPS induces changes in the pharmacokinetics of CPZ as a result of changes occurring in the biliary secretory system.

Original languageEnglish
Pages (from-to)2258-2261
Number of pages4
JournalAntimicrobial agents and chemotherapy
Volume39
Issue number10
DOIs
Publication statusPublished - 01-01-1995

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Cefoperazone
Lactams
Lipopolysaccharides
Anti-Bacterial Agents
Pharmacokinetics
Bile
Hepatobiliary Elimination
Cefazolin
Klebsiella pneumoniae
Biliary Tract
Intravenous Administration
Body Weight

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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title = "Effect of a bacterial lipopolysaccharide on biliary excretion of a β- lactam antibiotic, cefoperazone, in rats",
abstract = "Klebsiella pneumoniae O3 lipopolysaccharide (LPS) has been found to dramatically modify the pharmacokinetics of the β-lactam antibiotic cefazolin in rats. This study investigated the effect of LPS on the biliary excretion of the β-lactam antibiotic cefoperazone (CPZ) in rats. CPZ is known to he actively secreted into the bile by a carrier-mediated transport system. LPS (250 μg/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CPZ (20 mg/kg). The pharmacokinetic parameters of CPZ were estimated by a noncompartment model. LPS induced a significant decrease in the systemic clearance (by approximately 50{\%}) and an increase in the mean residence time of CPZ. Significant decreases were also seen in the bile flow rate and in the biliary recovery of unchanged CPZ in the LPS-treated rats. LPS tended to increase the proportion of urinary excretion of CPZ. LPS significantly decreased the biliary clearance (by approximately 55{\%}) and renal clearance (by approximately 35{\%}) of CPZ. However, no changes in the volume of distribution at steady state for CPZ were observed between the treatment groups. Our findings suggest that LPS induces changes in the pharmacokinetics of CPZ as a result of changes occurring in the biliary secretory system.",
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Effect of a bacterial lipopolysaccharide on biliary excretion of a β- lactam antibiotic, cefoperazone, in rats. / Haghgoo, S.; Hasegawa, T.; Nadai, M.; Wang, L.; Nabeshima, Toshitaka; Kato, N.

In: Antimicrobial agents and chemotherapy, Vol. 39, No. 10, 01.01.1995, p. 2258-2261.

Research output: Contribution to journalArticle

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