Pharmacokinetics of enoxacin and its penetration into bronchial secretions and lung tissue

Abstract

Pharmacokinetic data were obtained from four healthy volunteers after oral administration of a single 400 or 600 mg dose of enoxacin. Enoxacin was absorbed quickly and absorption was increased when enoxacin was ingested after a meal. Renal clearance of enoxacin and 4-oxo-enoxacin decreased after simultaneous administration of probenecid. In addition, pharmacokinetic parameters of enoxacin and its 4-oxo metabolite were determined for plasma and sputum from 19 patients treated with enoxacin, 400 or 600 mg bd, for a respiratory tract infection. The half-life of both enoxacin and 4-oxo-enoxacin was 5-6 h; during treatment with 400 and 600 mg bd, the plasma concentrations exceeded MIC values for most bacteria isolated in respiratory tract infections, including most Pseudomonas aeruginosa strains; Streptococcus pneumoniae was an exception. Diffusion from plasma to sputum was approximately 100%. Of an ingested dose, 60-65% was recovered in the urine in 24 h. In a third study, a single 600 mg dose of enoxacin was given to 15 patients undergoing thoracotomy. Subsequent lung tissue concentrations of enoxacin were significantly higher than plasma concentrations at the same time after ingestion.

Penetration of ofloxacin into human lung tissue following a single oral dose of 200 milligrams

“…Our finding of high concentrations of ofloxacin in lung tissue, amply exceeding those in serum, is thus in accordance with earlier reports (2,6). The same phenomenon of accumulation in lung tissue has been demonstrated for ciprofloxacin (3) and enoxacin (7).…”

Competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by probenecid

“…Its [6,18,19]. For several quinolones, such as norfloxacin [9], fleroxacin [10], enoxacin [11], levofloxacin [7,8] and gatifloxacin [6], a reduction in renal clearance with probenecid was found.…”

“…Probenecid has been reported to inhibit active transport of both anionic and cationic drug molecules at various sites in the body [3][4][5]. Furthermore, it is well known to decrease the renal secretion of numerous quinolones such as gatifloxacin [6],levofloxacin [7,8],norfloxacin [9],fleroxacin [10] and enoxacin [11]. Moxifloxacin and sparfloxacin are not affected by probenecid [12,13].…”

Concentrations of oral lomefloxacin in serum and bronchial mucosa

“…The bronchial mucosa is probably the main site of acute bacterial infection in patients with chronic bronchitis and bronchiectasis (5) and, therefore, it is reasonable to measure drug concentrations at this site. Several quinolones have been found to attain higher bronchial mucosal and lung tissue concentrations than simultaneous concentrations in serum (7,9,17). The aim of this study was, therefore, to assess the concentration of a new quinolone, lomefloxacin, in human bronchial mucosa.…”

“…The bronchial mucosa is probably the main site of acute bacterial infection in patients with chronic bronchitis and bronchiectasis (5) and, therefore, it is reasonable to measure drug concentrations at this site. Several quinolones have been found to attain higher bronchial mucosal and lung tissue concentrations than simultaneous concentrations in serum (7,9,17). The aim of this study was, therefore, to assess the concentration of a new quinolone, lomefloxacin, in human bronchial mucosa. Lomefloxacin is a fluoroquinolone with a broad spectrum of in vitro activity against clinically important gram-positive and gram-negative aerobes and anaerobes, including the majority of organisms responsible for lower respiratory tract infections, including Staphylococcus aureus (18).…”