Ofloxacin: its pharmacology, pharmacokinetics, and potential for clinical application

Ofloxacin is a 4-quinolone antibiotic with rapid bactericidal activity against a wide variety of organisms. Its proposed mechanism of activity is interference with DNA gyrase, an enzyme essential for the replication of bacterial DNA. In vitro activity of ofloxacin includes a variety of aerobic and anaerobic bacteria. Enteric gram-negative bacilli and cocci are generally sensitive to ofloxacin; nonaeruginosa strains of Pseudomonas are less so. Numerous bacterial pathogens of the gastrointestinal tract are also sensitive to the drug. Although its MIC values for gram-positive aerobic organisms are generally higher, ofloxacin's bactericidal activity against these organisms is considered by some to be adequate, and superior to that of most other fluoroquinolones. Ofloxacin is well absorbed after oral administration. Wide tissue and body fluid distribution is demonstrated. Urinary excretion is thought to be the primary route of elimination, with 80% of the dose recovered in the urine within 24 hours. The serum half-life ranges between 2.9 and 9 hours in a dose-dependent manner. Only modest accumulation is reported after multiple-dose administration. Clinical trials using daily dosages of 100-800 mg/day in single or divided doses have been reported in the treatment of a variety of conditions such as skin and soft tissue infections, tonsillitis, sexually transmitted disease, respiratory tract infections, cystitis, and complicated and uncomplicated urinary tract infections. English reports of these trials, however, are generally limited to abstract form, making evaluation of trial design difficult. Side effects most frequently encountered include gastrointestinal and central nervous system reactions.