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 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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
M. Nakashima, T. Uematsu, M. Kanamaru, O. Okazaki, and H. Hakusui. Jpn. J. Clin. Pharmacol. Ther. 23:515–520 (1992).
A. Kamiya, M. Yamashita, S. Takagi, S. Arakawa, and S. Kamidono. Chemotherapy 40(S-3):196–202 (1992).
F. Sörgel and M. Kinzig. Am. J. Med. 94(suppl 3A):56S–69S (1993).
I. M. Weiner, In J. Orloff and R. W. Berliner (eds.), Renal Physiology, American Physiological Society, Washington, D.C., 1973, pp. 521–554.
T. Ohtomo, H. Saito, N. Inotsume, M. Yasuhara, and K. Inui. J. Pharmacol. Exp. Ther. 276:1143–1148 (1996).
T. Okano, H. Maegawa, K. Inui, and R. Hori. J. Pharmacol. Exp. Ther. 255:1033–1037 (1990).
I. M. Weiner and L. Roth. J. Pharmacol. Exp. Ther. 216:516–520 (1981).
Y.-L. He, Y. Tanigawara, A. Kamiya, and R. Hori. J. Pharmacokin. Biopharm. 19:667–690 (1991).
Z. Dische and E. Borenfreund. J. Biol. Chem. 192:583–587 (1951).
P. M. Misiak, M. A. Eldon, R. D. Toothaker, and A. J. Sedman. J. Clin. Pharmacol. 33:53–56 (1993).
M. Gibaldi and D. Perrier. Pharmacokinetics, 2nd ed., Marcel Dekker, Inc., New York, 1982.
K. J. Ullrich, G. Rumrich, C. David, and G. Fritzsch. Pflügers Arch. 425:300–312 (1993).
T. Ooie, H. Suzuki, T. Terasaki, and Y. Sugiyama. J. Pharmacol. Exp. Ther. 278:590–596 (1996).
F. Thiebaut, T. Tsuruo, H. Hamada, M. M. Gottesman, I. Pastan, and M. C. Willingham. J. Histochem. Cytochem. 37:159–164 (1989).
F. Thiebaut, T. Tsuruo, H. Hamada, M. M. Gottesman, I. Pastan, and M. C. Willingham. Proc. Natl. Acad. Sci. U.S.A. 84:7735–7738 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yano, I., Ito, T., Takano, M. et al. Evaluation of Renal Tubular Secretion and Reabsorption of Levofloxacin in Rats. Pharm Res 14, 508–511 (1997). https://doi.org/10.1023/A:1012111902798
Issue Date:
DOI: https://doi.org/10.1023/A:1012111902798