Absorption and bioavailability
After a single 400 mg intravenous 1 hr infusion, peak concentrations of approximately 4.1 mg/L were reached in the plasma at the end of infusion which corresponds to a mean increase of approximately 26% relative to the oral administration. Exposure to drug in terms of AUC at a value of approximately 39 mg x h/L is only slightly higher compared to the exposure after oral administration (35 mg x h/L) in accordance with the absolute bioavailabilty of approximately 91%.

Following multiple intravenous dosing (1 hr infusion), peak and trough plasma concentrations at steady state (400 mg once daily) were between 4.1 to 5.9 and 0.43 to 0.84 mg/L, respectively. At steady-state the exposure to drug within the dosing interval is approximately 30% higher than after the first dose. In patients mean steady state concentrations of 4.4 mg/L were observed at the end of a 1 hr infusion.

Following oral administration Avelox is absorbed rapidly and almost completely. The absolute bioavailability amounts to approximately 91%.

Steady state is reached within 3 days. Following a 400 mg oral dose, peak concentrations of 3.1 mg/L are reached within 0.5 – 4 hrs. Peak and trough plasma concentrations at steady state were 3.2 and 0.6 mg/L, respectively.

Distribution
Avelox is distributed very rapidly to extravascular spaces. In vitro and ex vivo experiments over a range of 0.02 to 2 mg/L demonstrated approximately 45% protein binding, independent of drug concentration. Avelox is mainly bound to serum albumin. Due to this low value, high free peak concentrations >10 x MIC are observed.

Avelox reaches high concentrations in tissues like lung (epithelial fluid, alveolar macrophages, biotic tissue), the sinuses (maxillary and ethmoid sinus, nasal polypi) and inflamed lesions (cantharide blister fluid) where total concentrations exceeding those of the plasma concentrations are reached. High free drug concentrations are measured in interstitial body water (saliva, intramuscular, subcutaneous). In addition, high drug concentrations were detected in abdominal tissues and fluids.

The following table provides (geometric mean) peak concentrations of Avelox found in human tissues following oral and intravenous administration of a single 400 mg dose.

The peak concentrations and site versus plasma concentration ratios for various target tissues yielded comparable results for both modes of drug administration after a single dose of 400 mg Avelox.

Pharmacodynamics
In patients requiring hospitalization, AUC/MIC₉₀ greater than 125 and Cmax/MIC₉₀ of 8-10 are predictive for clinical cure. The following table provides the respective pharmaco- kinetic/pharmacodynamic (PK/PD) surrogates for intravenous administration of 400 mg Avelox calculated from single dose data.

Metabolism
Avelox undergoes Phase II biotransformation and balanced excretion via renal and biliary/fecal pathways as unchanged drug as well as in the form of a sulfo-compound (M1) and a glucuronide (M2). M1 and M2 are the only metabolites relevant in humans. Both metabolites are microbiologically inactive.

Elimination
Avelox is eliminated from plasma with a mean terminal half life of approximately 12 hours.