A prospective, multicentre study of moxifloxacin concentrations in the sinus mucosa tissue of patients undergoing elective surgery of the sinus

Abstract

A pharmacokinetic study was carried out to determine moxifloxacin concentrations in sinus tissue, after oral moxifloxacin 400 mg once daily for 5 days to patients with chronic sinusitis, undergoing elective sinus surgery. Patients were randomly allocated to one of seven treatment groups, in which tissues were sampled 2, 3, 4, 6, 12, 24 or 36 h post-dose. A control group with non-infected nasal polyps was also included. Forty-eight patients (13 female, 35 male, mean age 47.1 years) were allocated to one of each active treatment group (n = 42) or to the control group (n = 6). Tissue and plasma samples were taken simultaneously and stored frozen until assayed by HPLC. Thirty-nine patients were fully valid for pharmacokinetic analysis. The geometric mean moxifloxacin plasma concentration increased from 2.32 mg/L at 2 h to a maximum of 3.37 mg/L at 4 h post-dose, decreasing to 0.37 mg/L at 36 h post-dose. The moxifloxacin concentration in sinus mucosa was consistently greater than that in plasma being 4.56-5.73 mg/kg from 2 to 6 h and 2.81-1.25 mg/kg from 12 to 36 h post-dose. The elimination rates in plasma and sinus tissues were similar. The tissue/plasma ratio was c. 200% between 2 and 6 h, and up to 328.9% at 36 h. Results were similar whatever the site of tissue sampling (maxillary sinus, anterior ethmoid sinus or nasal polyps). Tissue levels exceeded the MIC(90) of all pathogens commonly causing acute sinusitis (e.g. 5-30 x MIC for Streptococcus pneumoniae: 0.25 mg/L). These results sup-port the use of moxifloxacin 400 mg once daily as a regimen for the treatment of sinus infections.

Fluoroquinolones compared with -lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials

“…Despite their inferior bacteriologic activity, our inclusion of ciprofloxacin and sparfloxacin in this meta-analysis may be meaningful, given that these 2 agents share certain pharmacokinetic properties with the newer respiratory fluoroquinolones, specifically with regard to drug penetration into the sinus mucosa. [33][34][35] In addition, from a safety standpoint, most of the adverse events observed with fluoroquinolones are thought to be related to a class effect rather than an agentspecific effect.…”

“…Although serious complications of sinusitis are rare among patients who receive appropriate treatment, 13 the lack of such complications in the populations evaluated in this metaanalysis could be attributed to the fact that patients with a greater likelihood of a complicated course of disease (e.g., those with a history of chronic sinusitis or recurrent acute sinusitis) were excluded from a considerable number of the trials, 21,25,26,[28][29][30]34 even though they are frequently encountered in routine clinical practice. In addition, in all but one of the included studies, 25 the duration of follow-up was limited to no more than 1 month after the end of therapy, which may have been inadequate for accurate estimation of the rates of recurrence and progression to chronic sinusitis.…”

Moxifloxacin in the Treatment of Acute Maxillary Sinusitis after First-Line Treatment Failure and Acute Sinusitis with High Risk of Complications

“…The concentration of moxifloxacin in sinus mucosa membranes is 2 -3 times higher than plasma concentrations. 23 These concentrations were assessed in patients whose local conditions -subacute sinusal foci, i.e., relatively mild inflammation -were comparable to those of patients included in our study. These local conditions have been demonstrated to have a significant impact on antibiotic diffusion 24 25 Currently, three sources of information on the safety of moxifloxacin are available: studies associated with clinical development; post-marketing surveillance studies; and reports collected in countries where it is being marketed.…”

Moxifloxacina: profilo farmacologico, terapeutico e farmacoeconomico

“…Le concentrazioni di moxifloxacina sono state misurate dopo singola dose orale di 400mg nei liquidi e tessuti polmonari di soggetti sottoposti a broncoscopia e nella mucosa dei seni nasali di pazienti trattati con 400mg/die e sottoposti ad intervento chirurgico [87,88]. Dopo singola dose orale (400mg) le concentrazioni di moxifloxacina nel secreto bronchiale, nel tessuto bronchiale e nei macrofagi alveolari raggiungono concentrazioni notevolmente più elevate di quelle sieriche anche dopo 24 ore dalla somministrazione (Figura 2).…”

“…Concentrazioni due-tre volte superiori a quelle sieriche sono state misurate nella mucosa dei seni mascellari, etmoidali e nei polipi nasali in soggetti trattati con dosi multiple di moxifloxacina 400mg/die e sottoposti ad intervento chirurgico [88].…”