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/AUCtotal-plasma ratios ranging from 0.38 to 0.55 and mean AUCinterstitial fluid/AUCfree-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.

New drugs to treat skin and soft tissue infections

“…Moreover, the concentrations of moxifloxacin in blister fluid were similar to its serum concentrations for at least 24 hours. Good penetration into subcutaneous adipose tissue, muscle, and bone has also been observed with moxifloxacin [28,29]. These concentrations exceed the MIC values for most clinically relevant bacterial pathogens associated with SSTIs and bone infections.…”

Moxifloxacin and Ciprofloxacin Protect Human Respiratory Epithelial Cells against Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae in Vitro

“…For limiting fluoroquinolone concentrations to the intracellular compartment, vesicles were washed five times with cell culture medium. The intracellular concentrations of moxifloxacin and ciprofloxacin was determined by high-pressure liquid chromatography (HPLC) [16].…”

“…Indeed, fluoroquinolone antibiotics penetrate very well into various tissues including the respiratory tract [16][17][18][19][20] and into phagocytic [21,22] and epithelial cells [23]. Here we sought to assess the bactericidal effect of ciprofloxacin on P. aeruginosa and H. influenzae and the bactericidal effect of moxifloxacin on S. pneumoniae and S. aureus in a respiratory cell culture infection model.…”

Quinolone Antibiotics: The Development of Moxifloxacin

“…The growing resistance of Gram-positive pathogens such as S. aureus or S. pyogenes, which, in addition to other bacteria, such as Streptococcus spp., coagulase-negative Staphylococcus, Enterococcus spp., Escherichia coli, Pseudomonas aeruginosa, Enterobacter spp., Proteus mirabilis, Klebsiella pneumoniae and Bacteroides fragilis, are considered to be the main cause of SSSI, presents increasing therapeutic problems. Due to their effective tissue penetration [199] and broad antibacterial spectrum, fluoroquinolones such as moxifloxacin provide welcome additional therapeutic alternatives for the treatment of dermatological infections [198,[200][201][202][203]. Compared to the other antibiotics, moxifloxacin has powerful in vitro activity against aerobic and anaerobic pathogens isolated from infected bite wounds (excluding the relatively resistant Fusobacterium spp.…”

“…Moxifloxacin penetrates rapidly into the tissues and body fluids and forms high concentrations in the target tissue; these remain higher than the MIC values for the most important pathogens over the entire dosage period of 24 h [199,224,225].…”