Penetration of moxifloxacin into peripheral compartments in humans

To characterize the penetration of moxifloxacin (BAY 12-8039) into peripher al target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, a n innovative clinical sampling technique. In addition, moxifloxacin concent rations were measured in cantharides-induced skin blisters, saliva, and cap illary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in a n open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min, An almost-comple te equilibration of the free unbound plasma fraction of moxifloxacin with t he interstitial space fluid was observed, with mean area under the concentr ation-time curve (AUC)(interstitial fluid)/AUC(total-) (plasma) ratios rang ing from 0.38 to 0.55 and mean AUC(interstitial fluid)/AUC(free-plasma) rat ios ranging from 0.81 to 0.86. The skin blister concentration/plasma concen tration ratio reached values above 1.5 after 24 h, indicating a preferentia l penetration of moxifloxacin into inflamed lesions. The moxifloxacin conce ntrations in saliva and capillary blood were similar to the corresponding l evels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isola tes are inhibited for most clinically relevant bacterial strains, notably i ncluding penicillin-resistant Streptococcus pneumoniae. These findings supp ort the use of moxifloxacin for the treatment of soft tissue and respirator y tract infections in humans.