[Penetration of azithromycin into human neutrophils: effect of hydrogen peroxide production].
BACKGROUND
The aim of this study was to evaluate the uptake of azythromycin at therapeutic concentrations by human polymorphonuclear leukocytes (PMN), as well as the effect of environmental temperature, pH, and cell viability on this uptake. The effect of azythromycin and other macrolides on hydrogen peroxide production by PMN was also assessed.


METHODS
Uptake of radiolabeled azythromycin by PMN was determined by a radiometric technique. Hydrogen peroxide production by PMN was measured by the phenol red method.


RESULTS
The intracellular concentrations achieved by azythromycin in PMN were 20 to 60 fold the extracellular ones, even at extracellular concentration of 0.125 mg/l. The uptake was significantly affected by low temperature, acid pH, and cell viability. Hydrogen peroxide production was not affected by the macrolides studied.


CONCLUSIONS
Azythromycin at therapeutical concentrations achieves high intracellular accumulation in human PMN. The effect of environmental temperature, pH and cell viability on uptake points out that a passive diffusion, with lysosome trapping, is the essential mechanism of azythromycin uptake by phagocytic cells. In spite of the high intracellular concentrations achieved by macrolides, hydrogen peroxide production by PMN is not affected by these compounds.
Rodríguez-Bano
J
J
Sección de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla.
Pascual
A
A
Ballesta
S
S
García
I
I
Perea
E J
EJ
D000900:Anti-Bacterial Agents / Q000378:metabolism; D017963:Azithromycin / Q000378:metabolism*; D002470:Cell Survival; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D009504:Neutrophils / Q000378:metabolism*; D013696:Temperature
D000900:Anti-Bacterial Agents; D017963:Azithromycin; D006861:Hydrogen Peroxide