Distribution kinetics of enoxacin and its metabolite oxoenoxacin in excretory fluids of healthy volunteers

Abstract

The distribution kinetics of enoxacin and its main metabolite oxoenoxacin in excretory fluids was investigated in 11 healthy volunteers. A single intravenous dose of 428 mg of enoxacin was given as a 1-h infusion. Serial samples of plasma, urine, saliva, nasal secretions, tears, and sweat were drawn and analyzed for enoxacin and oxoenoxacin by reversed-phase high-pressure liquid chromatography. Large differences in the concentration-time profiles of the excretory fluids analyzed were observed. Nasal secretions exhibited the highest enoxacin exposure, as assessed by the area under the concentration-time curve. Excretory fluid/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 urine and saliva and exhibited a higher renal clearance and a lower saliva exposure than the parent compound. In contrast to that of the metabolite, 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 sites. Because of distinct acidic and basic properties, the anionic oxometabolite significantly differs from the zwitterionic parent compound in its distribution characteristics.

Lachrymal Determinations: Methods and Updates on Biopharmaceutical and Clinical Applications

“…In patients, significant increases in lachrymal concentrations of minocycline were detected according to local inflammation. Similar results were found with azithromycin [110], ofloxacine [111] or enoxacin [112].…”

Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2

“…Plasma samples were analyzed for caffeine, 18 unchanged pefloxacin, 19 and unchanged enoxacin 20 by reversed‐phase HPLC assays. Concentrations of metabolites of caffeine or of quinolones were not determined in the vivo studies.…”

Saliva testing after single and chronic administration of dihydrocodeine

“…According to the pH-partition theory and the generally lower pH value in saliva compared to blood, a higher concentration of dihydrocodeine on the cellular and salivary side than in the intravasal space and a saliva-serum distribution greater than unity was to be expected [16,21]. The theoretical saliva/ serum concentration ratio for dihydrocodeine can be estimated by the equation of Matin et al [29].…”