Sparfloxacin

Sparfloxacin is a broad-spectrum antibacterial agent that inhibit DNA gyrase and topoisomerase IV and kills many of the types of bacteria that can infect the breathing airways and lungs and has been shown in a large number of clinical trials to be safe and effective for the treatment of bacterial infections. It is found to be more effective in vitro than other fluoroquinolones against some gram positive organisms (Streptococcus pneumoniae, Staphylococcus aureous), Mycobacteria and Chlamydia spp.Absorption: Quinoflox‚ is well absorbed following oral administration with an absolute oral bioavailability of 92%. The mean maximum plasma sparfloxacin concentration following a single 400-mg oral dose was approximately 1.3 (±0.2) µg/mL. The area under the curve following a single 400-mg oral dose was approximately 34 (±6.8) µg·hr/mL. Steady-state plasma concentration was achieved on the first day by giving a loading dose that was double the daily dose. Maximum plasma concentrations for a 200 mg dose were also achieved between 3 to 6 hours after administration with a mean of about 4 hours. Oral absorption of sparfloxacin is unaffected by administration with milk or food, including high fat meals. Concurrent administration of antacids containing magnesium hydroxide and aluminium hydroxide reduces the oral bioavailability of sparfloxacin by as much as 50%.Distribution: Upon reaching general circulation, Quinoflox‚ distributes well into the body, as reflected by the large mean steady-state volume of distribution (Vdss ) of 3.9 (±0.8) L/kg. Sparfloxacin exhibits low plasma protein binding in serum at about 45%. Sparfloxacin penetrates well into body fluids and tissues. Results of tissue and body fluid distribution studies demonstrated that oral administration of sparfloxacin produces sustained concentrations and that sparfloxacin concentrations in lower respiratory tract tissues and fluids generally exceed the corresponding plasma concentrations. The concentration of sparfloxacin in respiratory tissues (pulmonary parenchyma, bronchial wall, and bronchial mucosa) at 2 to 6 hours following standard oral dosing was approximately 3 to 6 times greater than the corresponding concentration in plasma. Concentrations in these respiratory tissues increase at up to 24 hours following dosing. Sparfloxacin is also highly concentrated into alveolar macrophages compared to plasma. Mean pleural effusion to plasma concentration ratios were 0.34 and 0.69 at 4 and 20 hours postdose, respectively.Metabolism: Quinoflox‚ is metabolised by the liver, primarily by phase II glucuronidation, to form a glucuronide conjugate. Its metabolism does not utilize or interfere with cytochrome-mediated oxidation, in particular cytochrome P450.Excretion: The total body clearance and renal clearance of Quinoflox‚ were 11.4 (±3.5) and 1.5 (±0.5) L/hr, respectively. Sparfloxacin is excreted in both the feces (50%) and urine (50%). Approximately 10% of an orally administered dose is excreted in the urine as unchanged drug in patients with normal renal function.