Penetration of moxifloxacin into peripheral compartments in humans

Abstract

To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an 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-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)(interstitial fluid)/AUC(total-plasma) ratios ranging from 0.38 to 0.55 and mean AUC(interstitial fluid)/AUC(free-plasma) ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels 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 isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant Streptococcus pneumoniae. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans.

FIG. 1

Profiles of time versus total-drug (open circles, solid line) and free-drug (open circles, dotted line) concentrations in plasma and interstitial fluid for muscle (solid triangles) and subcutaneous adipose tissue (open triangles) following administration of moxifloxacin (single p.o. dose of 400 mg [left panel] or single i.v. dose of 400 mg over 60 min [right panel]) in healthy volunteers (n = 12). The results are presented as means ± standard errors.

FIG. 2

Time versus plasma and saliva, capillary blood, and cantharides-induced skin blister fluid drug concentration profiles following administration of moxifloxacin (single p.o. dose of 400 mg [upper panel] or single i.v. dose of 400 mg over 60 min [lower panel] in healthy volunteers (n = 12). The results are presented as means ± standard errors.

FIG. 3

Time course of the interstitial fluid of muscle (solid triangles) or subcutaneous adipose tissue (open triangles), saliva (solid circles), and cantharides-induced skin blister fluid (solid squares) drug concentration/plasma drug concentration ratios of moxifloxacin for the experiments shown in Fig. 1 (left panel). The results are presented as means ± standard errors.