[Clinical pharmacology of ofloxacin: a new chemotherapeutic agent belonging to the gyrase inhibitor group]

Abstract

Ofloxacin (HOE 280, DL 8280, OFX) is a new broad-spectrum chemotherapeutic agent belonging to the group of the gyrase inhibitors. The tolerability and pharmacokinetics have been investigated for the dose range from 100 mg to 2 X 600 mg. The substance has proved to be well tolerated; investigation of the effects on renal enzymes after multiple dosing with 300 mg b.i.d. showed that the risk of nephrotoxicity is negligible. Ofloxacin is rapidly and almost completely absorbed. Cmax and AUC are dose-dependent. The favourable half-life--between 6 and 7 h, irrespective of the dose--results in prolonged serum concentrations. Food interaction is slight and of no clinical relevance. The penetration into tissue and body secretions is rapid, and high levels are reached. The main route of elimination is the kidneys. The urinary concentrations are dose-dependent; but the proportion of the dose excreted via the kidneys remains approximately constant, 80% or more of the dose being recovered as unchanged ofloxacin. The degree of metabolisation in humans is small and of no clinical relevance. The glucuronide of ofloxacin found in the bile together with the two metabolites detected in the urine account for at most 5% of the dose given. The favourable kinetic profile of ofloxacin means that the daily regimen required is two doses at most. This is confirmed by clinical findings to date.