The uptake of
NM394, a new
quinolone, by and its subsequent elution from human polymorphonuclear leukocytes were studied and compared with those of
ofloxacin and
ciprofloxacin. The kinetics of the uptake of
NM394 was similar to that of
ciprofloxacin. The maximum intracellular-to-extracellular concentration ratio was 12.3, compared with 8.6 for
ciprofloxacin and 4.9 for
ofloxacin at the extracellular concentration of 20 micrograms/ml. The elution of
NM394 from human polymorphonuclear leukocytes occurs relatively slowly; 5 min after the removal of extracellular
NM394, nearly 100% still remained in polymorphonuclear leukocytes, compared with
ofloxacin, which was so rapidly eluted that only 12% remained. The uptake of
NM394 was significantly decreased at 4 degrees C and by the presence of NaCN but was not affected by the presence of L-
glycine,
L-leucine,
L-serine,
adenosine, or NaF.
NM394 showed intracellular activity at a concentration of 0.1 microgram/ml that significantly reduced the number of phagocytosed Pseudomonas aeruginosa cells with 2 h of incubation. These results suggest that uptake of
NM394 by human polymorphonuclear leukocytes occurs via an active transport system differing from that of
ofloxacin, whose uptake is affected by the presence of L-
glycine and
L-leucine, and that once accumulated,
NM394 remains intracellularly active and participates in protection against
bacterial infection.