CLINICAL PHARMACOKINETICS OF SPARFLOXACIN

Sparfloxacin is a recently developed fluoroquinolone. The drug has shown potent antimicrobial activity against a wide range of Gram-positive and Gram-negative bacteria, glucose non-fermenters, anaerobes, Legionella spp., Mycoplasma spp., Chlamydia spp. and Mycobacterium spp. Methicillin-resistant Staphylococcus aureus is also susceptible to sparfloxacin. Plasma sparfloxacin concentrations reach a peak (C(max)) of approximately 0.7 mg/L at 3 to 5 hours after a 200mg oral dose. This is followed by a monophasic slow decrease, with an elimination half-life (t1/2) of 15 to 20 hours. The C(max) and area under the plasma concentration-time curve show dose-related increases. Food intake does not affect the absorption and pharmacokinetics of sparfloxacin. Sparfloxacin binds weakly to plasma protein (37%), and exhibits excellent tissue distribution and effective penetration into extracellular fluids. Concentrations of the drug in most tissues are similar to, or higher than, concomitant plasma concentrations. Sparfloxacin distributes slightly into cerebrospinal fluid. The drug is metabolised to a glucuronide. The urinary excretion of the unchanged drug accounts for 10 to 14% of the given dose. The ratio of Cn. values after multiple and single oral doses is 1.3 to 1.4, but other pharmacokinetic parameters of sparfloxacin are not influenced by multiple doses. Even in patients with severe renal failure, no significant prolongation of the half-life is observed after oral administration. Sparfloxacin appears unlikely to affect the pharmacokinetics of theophylline. Antacids containing aluminium hydroxide reduce the oral bioavailability of sparfloxacin by 25 to 35%. Probenecid does not affect sparfloxacin pharmacokinetics. The pharmacokinetic properties of sparfloxacin allow once-daily administration in the treatment of various infections.