Disposition and intracellular levels of moxifloxacin in human THP-1 monocytes in unstimulated and stimulated conditions.

Moxifloxacin uptake by human THP-1 monocytes was passive and initially linear and reached equilibrium after approximately 4 h. High intracellular concentrations were achieved and intracellular/extracellular [I/E] ratios were between 1925 and 4575 for the lowest concentration of 0.004 microg/ml at pH 7.4 and 6.9. The uptake of moxifloxacin was reduced by sodium fluoride, -azide, -cyanide, low temperature and low pH. However, the uptake was not affected by any of the ion channel blockers. Adenosine demonstrated marginal competition with moxifloxacin for uptake suggesting a nucleoside transporter may be involved. The sodium-ATPase pump when blocked, also retarded moxifloxacin uptake at 2 and 4 h. This I/E ratio was high compared with other macrolides and indicateed that the monocyte may contain sufficient moxifloxacin levels to conduct the antibiotic throughout systemic circulation to infection sites. Efflux from THP-monocytes was essentially complete after 2 h indicating no long term sequestering of the antibiotic occurred. Disposition of the antibiotic within the THP-1 monocytes showed large amounts present in the nucleus and cytoplasm in stimulated and unstimulated cells. Increased amounts of the drug were found in the THP-1 monocytes as well as the endoplasmic reticulum and the isolated phagosomes after stimulation by zymogen A, Staphylococcus aureus or Streptococcus pneumoniae.