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Muscle distribution of antimicrobial agents after a single intravenous administration to rats

Harumi Araki1, Naoko Ogake, Reiko Tsuneda

  • 1Research Laboratories, Toyama Chemical Co., Ltd., Japan. HARUMI_ARAKI@toyama-chemical.co.jp

Drug Metabolism and Pharmacokinetics
|December 25, 2004
PubMed

Insights

This study tracked fluoroquinolone and ceftazidime distribution in rat muscle tissue. Ceftazidime stays in the interstitial space, pazufloxacin distributes evenly, and ciprofloxacin/ofloxacin concentrate in cells.

Area of Science:

  • Pharmacokinetics and Drug Distribution
  • Biomedical Engineering
  • Microdialysis Techniques

Background:

  • Understanding drug distribution in tissues is crucial for optimizing antimicrobial therapy.
  • Muscle tissue penetration varies significantly between different antibiotic classes.
  • Previous studies established steady-state drug concentrations, but immediate post-administration distribution requires further investigation.

Purpose of the Study:

  • To evaluate the distribution of pazufloxacin, ciprofloxacin, ofloxacin (fluoroquinolones), and ceftazidime (beta-lactam) in rat muscle interstitial and intracellular spaces.
  • To compare unbound interstitial fluid concentrations with plasma concentrations shortly after intravenous administration.
  • To determine the primary site of distribution (interstitial vs. intracellular) for these antibiotics in muscle tissue.

Main Methods:

  • Muscle microdialysis was employed in rats following a single intravenous dose of the antibiotics.
  • Unbound interstitial fluid concentrations (C(isf,u)) were estimated using dialysate concentrations, in vitro permeability, and effective dialysis coefficients.
  • Total interstitial fluid concentrations (C(isf)) were calculated using plasma protein binding and interstitial-to-plasma albumin ratios, then compared to homogenized muscle concentrations (C(m)).

Main Results:

  • Unbound concentrations in muscle interstitial fluid (C(isf,u)) approximated unbound plasma concentrations for all tested drugs.
  • Ceftazidime showed higher interstitial fluid concentration than homogenized muscle concentration (C(isf) > C(m)).
  • Pazufloxacin exhibited near-equal distribution between interstitial fluid and muscle cells (C(isf) ≈ C(m)).
  • Ciprofloxacin and ofloxacin concentrations were lower in interstitial fluid than homogenized muscle (C(isf) < C(m)), indicating intracellular accumulation.

Conclusions:

  • Ceftazidime predominantly distributes into the muscle's interstitial space.
  • Pazufloxacin distributes equally between interstitial and intracellular compartments.
  • Ciprofloxacin and ofloxacin primarily distribute into muscle tissue cells, with limited interstitial penetration.
  • These findings highlight differential tissue distribution patterns influencing antibiotic efficacy and dosing strategies.

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