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Related Experiment Videos

Granulocyte colony-stimulating factor enhances endotoxin-induced decrease in biliary excretion of the antibiotic

M Nadai1, I Matsuda, L Wang

  • 1Laboratory of Clinical Pharmacology and Therapeutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502, Japan.

Antimicrobial Agents and Chemotherapy
|September 16, 1998
PubMed
Summary

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Granulocyte colony-stimulating factor (G-CSF) worsens the lipopolysaccharide (LPS)-induced reduction in cefoperazone (CPZ) biliary excretion in rats. Leukocytes appear to play a key role in this detrimental effect.

Area of Science:

  • Pharmacology
  • Toxicology
  • Immunology

Background:

  • Endotoxin (lipopolysaccharide, LPS) from Klebsiella pneumoniae significantly reduces cefoperazone (CPZ) biliary excretion in rats.
  • CPZ is a beta-lactam antibiotic primarily eliminated via the bile through the anion transport system.
  • Human recombinant granulocyte colony-stimulating factor (G-CSF) has shown benefits in experimental inflammation models.

Purpose of the Study:

  • To investigate the effect of G-CSF on the pharmacokinetics and biliary excretion of CPZ in rats previously treated with LPS.
  • To understand the role of G-CSF in modulating drug excretion during endotoxemia.

Main Methods:

  • Rats were administered LPS intravenously, followed by cefoperazone (CPZ) administration.
  • G-CSF was administered via subcutaneous injection for 3 days and a single intravenous dose before LPS injection.

Related Experiment Videos

  • Systemic and biliary clearances, bile flow rate, and peripheral blood cell counts were measured.

    • Main Results:

    • LPS significantly decreased CPZ systemic and biliary clearances and bile flow rate.
    • G-CSF pretreatment exacerbated the LPS-induced reductions in CPZ clearance and bile flow.
    • G-CSF increased total leukocyte counts, while LPS decreased them; G-CSF counteracted the LPS effect on leukocytes.

    Conclusions:

    • G-CSF exhibits a detrimental effect on the LPS-induced decrease in CPZ biliary secretion.
    • Leukocytes are implicated as a significant factor in the mechanism underlying G-CSF's adverse effect on CPZ excretion during LPS challenge.