DISTRIBUTION KINETICS OF ENOXACIN AND ITS METABOLITE OXOENOXACIN IN EXCRETORY FLUIDS OF HEALTHY-VOLUNTEERS

The distribution kinetics of enoxacin and its main metabolite oxoenoxa cin in excretory fluids was investigated in 11 healthy volunteers, A s ingle intravenous dose of 428 mg of enoxacin was given as a l-h infusi on, Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reve rsed-phase high-pressure liquid chromatography, Large differences in t he concentration-time profiles of the excretory fluids analyzed were o bserved, Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve, Excretory flu id/plasma area under the concentration-time curve ratios were found to be 1.67 +/- 0.36 for nasal secretions, 0.76 +/- 0.28 for saliva, 0.25 +/ 0.07 for sweat, and 0.23 +/- 0.11 for tears, The elimination half- life of enoxacin from sweat (8.27 +/- 2.63 h) was significantly longer than that for plasma (5.10 +/- 0.46 h), Oxoenoxacin was detected in u rine and saliva and exhibited a higher renal clearance and a lower sal iva exposure than the parent compound, In contrast to that of the meta bolite, distribution of enoxacin in saliva was found to be time and pH dependent, In conclusion, our study revealed considerable differences in the distribution kinetics of enoxacin among various excretory site s, Because of distinct acidic and basic properties, the anionic oxomet abolite significantly differs from the zwitterionic parent compound in its distribution characteristics.