The Absorption and Disposition of Enoxacin in Healthy Subjects

Abstract

Enoxacin is a new orally active, synthetic broad‐spectrum antibacterial drug of the fluorinated quinolone class. The pharmacokinetics and renal handling of this drug have not been thoroughly investigated, in particular, with specific analytical methodology. Sixteen healthy, young subjects received a single 400‐mg oral dose of enoxacin after an overnight fast and multiple blood samples and all urine were collected for 33 hours. Enoxacin in plasma and urine and oxo‐enoxacin in urine were determined by a high‐performance liquid chromatographic method. Enoxacin was absorbed rapidly, with t_max values ranging from 0.5 to 2.5 hours. The variability in the AUC values of 35% was reduced to 23% when variations in body weight were taken into consideration. The terminal half‐life ranged from 4.2 to 6.8 hours and the unbound fraction in plasma was 0.33 ± 0.07. In urine, 44 ± 9% of the dose was recovered as unchanged enoxacin and 5.4 ± 3.9% as oxo‐enoxacin; there was no evidence of conjugates of enoxacin in urine. Renal clearance of enoxacin was 230 ± 92 mL/min, with 17 ± 8% of this being due to glomerular filtration and 83 ± 8% being due to tubular secretion. These data indicate that the major potential drug interactions affecting enoxacin disposition are likely with drugs competing for renal proximal tubular secretion and hepatic elimination. These conclusions regarding enoxacin are likely to be applicable to the fluorinated quinolones in general.