title: Uptake of quinolones by in-vitro human monocyte derived macrophages.
abstract: We have developed an in-vitro model of monocyte-derived macrophage (MDMphi) to compare fluoroquinolone uptake in monocytes and derived macrophages. Monocyte-derived macrophages were obtained in-vitro by cultivating freshly isolated monocytes for seven days in RPMI 1640 medium, containing foetal calf serum and Rhu granulocyte-macrophage colony stimulating factor. Final suspensions contained 95% viable cells and 63% macrophages. Intramacrophagic accumulation of ciprofloxacin, ofloxacin or sparfloxacin was measured at equilibrium after 30-min incubation in the presence of 16-18 microg mL(-1) antibiotic. The results revealed low intracellular accumulation of ofloxacin in MDMphi (intracellular/extracellular ratio: IC/EC = 1.7). Ciprofloxacin and sparfloxacin uptake was significantly higher. The IC/EC ratios were only slightly increased in macrophages when compared with monocytes under the same experimental conditions. These results suggest that maturation of monocyte to macrophage has only a limited effect on basal quinolone uptake. Monocytic maturation cannot explain the important differences between fluoroquinolone accumulation in monocytes and tissue macrophages. Cell activation may be a greater determinant.
authors.affiliation: Laboratory of Pharmacokinetics and Clinical Pharmacy, University Victor Ségalen-Bordeaux II, France.
authors.forename: M
authors.initials: M
authors.lastname: Dorian
authors.forename: J
authors.initials: J
authors.lastname: Grellet
authors.forename: M C
authors.initials: MC
authors.lastname: Saux
mesh_terms: D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D024841:Fluoroquinolones; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D016178:Granulocyte-Macrophage Colony-Stimulating Factor