I Yano1, T Ito, M Takano, K Inui. 1. Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Japan.
Abstract
PURPOSE: Levofloxacin, a quinolone antibacterial drug, is a zwitterion at physiological pH. We examined the effect of cationic and anionic drugs on renal excretion of levofloxacin by means of in vivo clearance to characterize the mechanisms of renal excretion of this drug. METHODS: In vivo clearance was studied in male Wistar albino rats. A bolus dose of 2.85 mg/kg of levofloxacin was administered, followed by a constant infusion of 7.08 micrograms/min. Cimetidine, tetraethylammonium, or p-aminohippurate was administered as a bolus and incorporated into the infusion solution. After reaching steady state, urine and blood concentrations were measured, and pharmacokinetic parameters were calculated. RESULTS: Renal clearance was 2.56 +/- 0.42 ml/min in control, which accounted for 34% of the total body clearance. Renal clearance was significantly decreased to 0.83 +/- 0.25 ml/min by cimetidine (p < .05), corresponding to 32% of the control value. The cationic drug, tetraethyl-ammonium also reduced the renal clearance of levofloxacin, but the effect of the anionic drug, p-aminohippurate, was slight. The clearance ratio of levofloxacin, which was calculated by renal clearance divided by the plasma unbound fraction and the glomerular filtration rate, was 1.60 +/- 0.38 in the control and it was decreased to 0.68 +/- 0.17 and 1.11 +/- 0.22 by cimetidine and tetraethylammonium, respectively. CONCLUSIONS: The present results suggest that the renal excretion of levofloxacin in rats involves tubular secretion and reabsorption, in addition to glomerular filtration, and that tubular secretion is inhibited by cimetidine.
PURPOSE:Levofloxacin, a quinolone antibacterial drug, is a zwitterion at physiological pH. We examined the effect of cationic and anionic drugs on renal excretion of levofloxacin by means of in vivo clearance to characterize the mechanisms of renal excretion of this drug. METHODS: In vivo clearance was studied in male Wistar albino rats. A bolus dose of 2.85 mg/kg of levofloxacin was administered, followed by a constant infusion of 7.08 micrograms/min. Cimetidine, tetraethylammonium, or p-aminohippurate was administered as a bolus and incorporated into the infusion solution. After reaching steady state, urine and blood concentrations were measured, and pharmacokinetic parameters were calculated. RESULTS: Renal clearance was 2.56 +/- 0.42 ml/min in control, which accounted for 34% of the total body clearance. Renal clearance was significantly decreased to 0.83 +/- 0.25 ml/min by cimetidine (p < .05), corresponding to 32% of the control value. The cationic drug, tetraethyl-ammonium also reduced the renal clearance of levofloxacin, but the effect of the anionic drug, p-aminohippurate, was slight. The clearance ratio of levofloxacin, which was calculated by renal clearance divided by the plasma unbound fraction and the glomerular filtration rate, was 1.60 +/- 0.38 in the control and it was decreased to 0.68 +/- 0.17 and 1.11 +/- 0.22 by cimetidine and tetraethylammonium, respectively. CONCLUSIONS: The present results suggest that the renal excretion of levofloxacin in rats involves tubular secretion and reabsorption, in addition to glomerular filtration, and that tubular secretion is inhibited by cimetidine.
Authors: Larry A Bauer; Douglas J Black; Jennifer S Lill; Julie Garrison; Vidmantas A Raisys; Thomas M Hooton Journal: Antimicrob Agents Chemother Date: 2005-04 Impact factor: 5.191