Pharmacokinetics of the Quinolones in Volunteers: a Proposed Dosing Schedule

The pharmacokinetics and tissue penetration of five quinolones into inflammatory exudate were studied in healthy volunteers. The compounds studied were norfloxacin (400 mg orally), enoxacin (400 mg intravenously and 600 mg orally), ciprofloxacin (100 mg intravenously and 500 mg orally), ofloxacin (600 mg orally), and pefloxacin (400 mg intravenous). Orally administered ofloxacin and ciprofloxacin were the most rapidly absorbed (time to maximal serum level, 1.2 hours) and enoxacin the least (1.9 hours). The serum levels attained were highest in the case of ofloxacin (after an allowance was made for the higher dose administered). The serum elimination half-lives were as follows: norfloxacin, 3.75 hours; ciprofloxacin, 3.9 hours (oral) and 4.0 hours (intravenous); ofloxacin, 7.0 hours; enoxacin, 6.2 hours (oral) and 5.1 hours (intravenous); and pefloxacin, 10.5 hours. All agents penetrated well into a mild inflammatory exudate. The 24-hour recovery rate from urine was 62% for oral enoxacin, 46.4% for intravenous enoxacin (plus 12.2% for oxo-enoxacin), 27% for norfloxacin, 30.6% for oral ciprofloxacin, 75.7% for intravenous ciprofloxacin, 73% for ofloxacin, and 4.9% for pefloxacin (plus 9.2% for the norfloxacin metabolite and 17.8% for pefloxacin N-oxide). A dosing schedule for the quinolones was proposed on the basis of pharmacokinetic parameters and microbiologic activity.