Pharmacokinetics of ofloxacin. An overview

Ofloxacin pharmacokinetics after oral and parenteral doses were investigated in healthy young and geriatric volunteers and renally impaired patients. After oral administration of single 100- to 600-mg doses to healthy younger volunteers, renal recovery indicates that the amount absorbed increases linearly from 100 to 600 mg. More than 70 percent of an oral dose is recovered in the urine as unchanged ofloxacin, and only minimal amounts, less than 5 percent of the dose, are recovered as the metabolites, desmethyl ofloxacin and ofloxacin N-oxide. After multiple (twice daily) oral administration of 400-mg doses to younger and older (65 to 81 years) healthy volunteers, a modest accumulation (i.e., maximal concentration increased about 50 percent), as predicted by single-dose data, is observed, and steady-state is achieved within 48 hours of the initiation of twice-daily dosing. In the young and elderly, ofloxacin is eliminated with a half-life of five to seven hours, independent of dose. In the renally impaired, however, there is a linear correlation between the half-life of ofloxacin and creatinine clearance, and this requires dose adjustment when the creatinine clearance rate is less than 50 ml/minute. The pharmacokinetics of ofloxacin also were investigated after intravenous administration of single 200- and 400-mg doses and multiple twice-daily 400-mg doses. After intravenous dosing, ofloxacin exhibits a pharmacokinetic profile similar to that seen after oral dosing, which supports the almost total oral absorption and the interchangeability of both forms of therapy. The pharmacokinetics of the compound indicate that, except for cases of renal impairment, little or no dosage adjustment is necessary.