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.
Hall
Iris H
IH
Division of Medicinal Chemistry, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7360, USA. iris_hall@unc.edu
Schwab
Ute E
UE
Ward
E Stacy
ES
Ives
Timothy
T
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001372:Aza Compounds / Q000493:pharmacokinetics*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D024841:Fluoroquinolones; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D000077266:Moxifloxacin; D011804:Quinolines / Q000493:pharmacokinetics*; D019810:Sodium Azide / Q000494:pharmacology; D012966:Sodium Cyanide / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013696:Temperature
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D012969:Sodium Fluoride; D019810:Sodium Azide; D012966:Sodium Cyanide; D000077266:Moxifloxacin