Pharmacokinetics and safety of single rising doses of ofloxacin in healthy volunteers

Abstract

The pharmacokinetics, safety, and disposition of the new antimicrobial fluoroquinolone ofloxacin were evaluated after oral administration in 14 healthy, male volunteers in a double-blind, placebo-controlled study. Ofloxacin was administered as 100-, 300-, and 600-mg doses separated by 1 week. Plasma and urine concentrations after each administration were measured using a sensitive and specific high-performance liquid chromatographic procedure. The distribution of ofloxacin was modeled using a two-compartment open-body model with first-order absorption. Maximum plasma concentrations and area under the plasma concentration versus time curve increased in a linear, dose-proportional manner over the range studied. At all levels, within 36 hours after administration, approximately 70% of the dose was recovered in urine as unchanged ofloxacin and only minimal amounts (less than 4%) as metabolites. No significant changes in the distribution or elimination of the compound were found over the 6-fold dose range. No major laboratory toxicities or clinically significant adverse effects were noted in either the ofloxacin or placebo group.