Pharmacokinetics of ofloxacin and the effect on the faecal flora of healthy volunteers.

Pharmacokinetic studies using a new oral quinolone ofloxacin were carried out in 12 healthy volunteers. The mean Cmax was 2.7 mg/l after the first dose of 200 mg ofloxacin rising to 3.4 mg/l after the seventh dose. The Tmax was between 1-2 h and the serum half life 5 h. Saliva concentrations matched serum levels but the absolute values were lower. Urinary concentrations ranged from 141 to 330 mg/l and the 12 h excretion was 62% after the seventh dose. Faecal concentrations were high and persisted for up to five days after the last dose. The major effect of ofloxacin on the faecal flora was the rapid and complete elimination of aerobic Gram-negative bacilli. Streptococci were generally increased but there was no change in the total anaerobic bacterial count. Pre-treatment composition of the faecal flora was re-established between 3 and 26 days after the last dose. Ofloxacin was well tolerated by the volunteers and only two complained of significant side effects, gastrointestinal disturbance and insomnia. Ofloxacin is a valuable addition to the range of antimicrobial agents available for the oral treatment of bacterial infection.