Pharmacokinetics and tissue distribution of ofloxacin in human subjects during a multiple dose regimen

The pharmacokinetics of ofloxacin was studied in normal male volunteers selected from a student population. The aim of this study was to ascertain whether ofloxacin accumulated in plasma after administering six oral doses of the drug. The drug was administered in 300 mg tablets at intervals of 12 h for a total period of 72 h. The results clearly demonstrated that a modest accumulation of ofloxacin was observed between the first and second oral intake of the drug (R = 1.4); thereafter a steady-state plasma concentration was maintained at all time periods tested during the study. Furthermore, there was a broad fluctuation of approximately 80% between the Cmax and Cmin in the plasma levels of the drug during a 12-hour dosing interval. Hence demonstrating that a constant dose, repeatedly administered at a constant time interval of 12 h, ensured a broad range of concentrations of ofloxacin plasma, bile and other tissues which should favour the therapeutic success of the drug. There was agreement between the results of these studies and those in hospitalized patients suffering from severe infections. Analysis of ofloxacin after multiple dosing regimens in these patients showed measurable concentrations of the drug in the various tissues examined; hence suggesting a relative good bioavailability of the drug, which presumably reflected the high degree of success rates in these patients.