caa a22 4500 477127339 CHVBK 20180405111653.0 cr unu---uuuuu 170330e19970401xx s 000 0 eng 10.1023/A:1012111902798 doi (NATIONALLICENCE)springer-10.1023/A:1012111902798 Evaluation of Renal Tubular Secretion and Reabsorption of Levofloxacin in Rats [Elektronische Daten] [Ikuko Yano, Tatsuya Ito, Mikihisa Takano, Ken-ichi Inui] 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 μg/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, tetraethylammonium 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. Plenum Publishing Corporation, 1997 levofloxacin nationallicence quinolone antibacterial drugs nationallicence renal secretion nationallicence organic cation transport nationallicence Yano Ikuko Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut Ito Tatsuya Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut Takano Mikihisa Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut Inui Ken-ichi Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 508-511 0724-8741 14:4<508 1997 14 11095 https://doi.org/10.1023/A:1012111902798 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012111902798 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yano Ikuko Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut NATIONALLICENCE 700 1- Ito Tatsuya Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut NATIONALLICENCE 700 1- Takano Mikihisa Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut NATIONALLICENCE 700 1- Inui Ken-ichi Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, 606-01, Sakyo-ku, Kyoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/4(1997-04-01), 508-511 0724-8741 14:4<508 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer