Safety and pharmacokinetics of multiple doses of intravenous ofloxacin in healthy volunteers. Antimicrob. Agents Chemother

The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons of mean harmonic half-lives, the areas under the concentration-time curve from 0 to 12 and 0 to 60 h, clearance, and apparent volume of distribution (area method) revealed that the pharmacokinetics of ofloxacin are dose independent. Both ofloxacin dosage regimens appeared to be reasonably well tolerated. The two dosage regimens of ofloxacin, 200 or 400 mg every 12 h, appear to be safe and provide serum drug concentrations in excess of the MICs for most susceptible pathogens over the entire dosing interval. Ofloxacin is a synthetic carboxyquinolone antimicrobial agent which exhibits broad-spectrum in vitro bactericidal activities against gram-positive and gram-negative aerobes (5). The clinical efficacy of ofloxacin has been documented in patients with respiratory tract, upper and lower urinary tract, and skin and soft tissue infections and gonococcal and nongonococcal urethritis (5, 8). In December 1990, the oral tablet formulation of ofloxacin was approved by the U.S. Food and Drug Administration, and marketing commence