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Comparative penetration of lomefloxacin and other quinolones into human phagocytes
Abstract:
The penetration of lomefloxacin into human polymorphonuclear leukocytes (PMNs) and peritoneal macrophages (PMphis) was evaluated using a fluorometric assay. Lomefloxacin reached high intracellular concentrations into PMNs at extracellular concentrations of 2 and 5 mg/L (cellular to extracellular concentration ratio [C/E] greater than 4). At the same conditions (20 minutes incubation; extracellular concentrations: 2 mg/L) lomefloxacin uptake by human PMNs (C/E: 7.9 +/- 2.6) was slightly higher than those of norfloxacin (C/E 5.1 +/- 1.8), ciprofloxacin (C/E: 6.2 +/- 2.0), and ofloxacin (C/E 7.1 +/- 2.6). Lomefloxacin penetration into human PMphis was significantly lower than PMNs but still with C/E ratios greater than 4. Entry of lomefloxacin into phagocytes was not affected by cell viability but was environmental-temperature dependent. It is concluded that lomefloxacin and the other quinolones evaluated reach high intracellular concentrations in human phagocytic cells.
Insights
Lomefloxacin effectively penetrates human phagocytic cells, reaching high intracellular concentrations in polymorphonuclear leukocytes (PMNs) and peritoneal macrophages (PMphis). This fluoroquinolone demonstrates potent uptake, exceeding that of other tested quinolones in PMNs.
Area of Science:
- Pharmacology
- Cell Biology
- Infectious Diseases
Background:
- Fluoroquinolones are crucial antibiotics for treating bacterial infections.
- Understanding intracellular drug concentrations is vital for efficacy against intracellular pathogens.
- Human phagocytic cells, like PMNs and macrophages, are key in host defense.
Purpose of the Study:
- To quantify the penetration of lomefloxacin into human polymorphonuclear leukocytes (PMNs) and peritoneal macrophages (PMphis).
- To compare lomefloxacin's intracellular uptake with other fluoroquinolones (norfloxacin, ciprofloxacin, ofloxacin).
- To investigate factors influencing lomefloxacin entry into phagocytes.
Main Methods:
- A fluorometric assay was employed to measure lomefloxacin concentrations.
- Human PMNs and PMphis were incubated with varying extracellular drug concentrations.
- Cellular to extracellular concentration ratios (C/E) were calculated to assess drug penetration.
Main Results:
- Lomefloxacin achieved high intracellular concentrations in PMNs, with C/E ratios exceeding 4 at 2 and 5 mg/L.
- Lomefloxacin uptake in PMNs (C/E: 7.9) was comparable or slightly higher than norfloxacin, ciprofloxacin, and ofloxacin.
- Penetration into PMphis was lower than PMNs but still significant (C/E > 4).
- Lomefloxacin entry was temperature-dependent but not affected by cell viability.
Conclusions:
- Lomefloxacin and other evaluated quinolones achieve substantial intracellular concentrations in human phagocytic cells.
- High intracellular accumulation suggests potential for effective treatment of infections involving these cells.
- The findings support the role of lomefloxacin in combating intracellular bacterial infections.