Abstract
Purpose. The aim of this study was to clarify the effects of renal failure on intestinal secretion of quinolone antibacterial drugs.
Methods. Pharmacokinetics of grepafloxacin, levofloxacin, and ciprofloxacin in cisplatin-induced acute renal failure (ARF) rats were evaluated, and intestinal and biliary clearance studies were examined. Transport experiments using culture cells were performed.
Results. The bioavailability of grepafloxacin in ARF rats was 1.2-fold higher than that in normal rats. On the other hand, the bioavailability of ciprofloxacin in ARF rats was markedly decreased to half of that in normal rats, and that of levofloxacin was not changed. Intestinal clearance of grepafloxacin in ARF rats was 75% of that in normal rats, whereas that of ciprofloxacin was 1.4-fold higher than in normal rats, and that of levofloxacin was comparable between normal and ARF rats. Transport experiments using P-glycoprotein-expressing LLC-GA5-COL150 cells and human intestinal Caco-2 cells suggested that grepafloxacin and levofloxacin were substrates of P-glycoprotein and that ciprofloxacin was not, and that intestinal secretion of ciprofloxacin was mediated by a specific transport system distinct from organic cation and anion transporters and multidrug resistance-associated protein 2.
Conclusions. Cisplatin-induced ARF differentially modulated the bioavailability and intestinal secretion of quinolones in rats.
Similar content being viewed by others
references
J. S. Wolfson and D. C. Hooper. Fluoroquinolone antibacterial agents. Clin. Microbiol. Rev. 2:378-424 (1989).
F. Sörgel, U. Jaehde, K. G. Naber, and U. Stephan. Pharmacokinetics disposition of quinolones in human body fluids and tissues. Clin. Pharmacokinet. 16(Suppl. 1):5-24 (1989).
C. Efthymiopoulos, S. L. Bramer, and A. Maroli. Pharmacokinetics of grepafloxacin after oral administration of single and repeat doses in healthy young males. Clin. Pharmacokinet. 33(Suppl. 1):1-8 (1997).
D. N. Fish and A. T. Chow. The clinical pharmacokinetics of levofloxacin. Clin. Pharmacokinet. 32:101-119 (1997).
F. Sörgel, K. G. Naber, U. Jaehde, A. Reiter, R. Seelman, and G. Sigl. Gastrointestinal secretion of ciprofloxacin. Am. J. Med. 87:62S-65S (1989).
G. R. Granneman, R. Braeckman, J. Kraut, S. Shupien, and J. C. Craft. Temafloxacin pharmacokinetics in subject with normal and impaired renal function. Antimicrob. Agents Chemother. 35:2345-2351 (1991).
H. Yamaguchi, I. Yano, Y. Hashimoto, and K. Inui. Secretory mechanisms of grepafloxacin and levofloxacin in the human intestinal cell line Caco-2. J. Pharmacol. Exp. Ther. 295:360-366 (2000).
K. Naruhashi, I. Tamai, N. Inoue, H. Muraoka, Y. Sai, N. Suzuki, and A. Tsuji. Active intestinal secretion of new quinolone antimicrobials and the partial contribution of P-glycoprotein. J. Pharm. Pharmacol. 53:699-709 (2001).
M. E. Cavet, M. West, and N. L. Simmons. Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells. Br. J. Pharmacol. 121:1567-1578 (1997).
N. M. Griffiths, B. H. Hirst, and N. L. Simmons. Active intestinal secretion of the fluoroquinolone antibacterials ciprofloxacin, norfloxacin and pefloxacin; a common secretory pathway? J. Pharmacol. Exp. Ther. 269:496-502 (1994).
S. Dautrey, K. Felice, A. Petiet, B. Lacour, C. Carbon, and R. Farinotti. Active intestinal elimination of ciprofloxacin in rats: modulation by different substrates. Br. J. Pharmacol. 127:1728-1734 (1999).
J. Fabre and L. Balant. Renal failure, drug pharmacokinetics and drug action. Clin. Pharmacokinet. 1:99-120 (1976).
H. Katayama, J. Fujiwara, M. Yasuhara, K. Okumura, and R. Hori. Increased availability of propranolol in rats with uranyl nitrate-induced acute renal failure. J. Pharmacobiodyn. 7:536-544 (1984).
H. Okabe, Y. Hashimoto, and K. Inui. Pharmacokinetics and bioavailability of tacrolimus in rats with experimental renal dysfunction. J. Pharm. Pharmacol. 52:1467-1472 (2000).
W. J. Tilstone and A. Fine. Furosemide kinetics in renal failure. Clin. Pharmacol. Ther. 23:644-650 (1978).
R. Rohwedder, T. Bergan, S. B. Thorsteinsson, and H. Scholl. Transintestinal elimination of ciprofloxacin. Chemotherapy 36:77-84 (1990).
S. Dautrey, L. Rabbaa, D. Laouari, B. Lacour, C. Carbon, and R. Farinotti. Influence of renal failure on intestinal clearance of ciprofloxacin in rats. Antimicrob. Agents Chemother. 43:678-680 (1999).
H. Akiyama, Y. Abe, M. Koike, K. Kyuushiki, N. Fujio, M. Odomi, F. Mukai, and K. Ohmori. Pharmacokinetics of grepafloxacin (I): absorption, distribution and excretion after oral administration of grepafloxacin in animals as determined by HPLC. Jpn. J. Chemother. 43(S-1):99-106 (1995).
T. Ohtomo, H. Saito, N. Inotsume, M. Yasuhara, and K. Inui. Transport of levofloxacin in a kidney epithelial cell line, LLC-PK1: interaction with organic cation transporters in apical and basolateral membranes. J. Pharmacol. Exp. Ther. 276:1143-1148 (1996).
K. Naora, Y. Katagiri, N. Ichikawa, M. Hayashibara, and K. Iwamoto. A possible reduction in the renal clearance of ciprofloxacin by fenbufen in rats. J. Pharm. Pharmacol. 42:704-707 (1990).
K. Inui, M. Yamamoto, and H. Saito. Transepithelial transport of oral cephalosporins by monolayers of intestinal cell line Caco-2: specific transport systems in the apical and basolateral membranes. J. Pharmacol. Exp. Ther. 261:195-201 (1992).
Y. Tanigawara, N. Okamura, M. Hirai, M. Yasuhara, K. Ueda, N. Kioka, T. Komano, and R. Hori. Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J. Pharmacol. Exp. Ther. 263:840-845 (1992).
T. Ito, I. Yano, K. Tanaka, and K. Inui. Transport of quinolone antibacterial drugs by human P-glycoprotein expressed in a kidney epithelial cell line, LLC-PK1. J. Pharmacol. Exp. Ther. 282:955-960 (1997).
S. Masuda, H. Saito, H. Nonoguchi, K. Tomita, and K. Inui. mRNA distribution and membrane localization of the OAT-K1 organic anion transporter in rat renal tubules. FEBS Lett. 407:127-131 (1997).
H. Yamaguchi, I. Yano, H. Saito, and K. Inui. Pharmacokinetic role of P-glycoprotein in oral bioavailability and intestinal secretion of grepafloxacin in vivo. J. Pharmacol. Exp. Ther. 300:1063-1069 (2002).
K. Naruhashi, I. Tamai, N. Inoue, H. Muraoka, Y. Sai, N. Suzuki, and A. Tsuji. Involvement of multidrug resistance-associated protein 2 in intestinal secretion of grepafloxacin in rats. Antimicrob. Agents Chemother. 46:344-349 (2002).
C. Veau, C. Leroy, H. Banide, D. Auchère, S. Tardivel, R. Farinotti, and B. Lacour. Effect of chronic renal failure on the expression and function of rat intestinal P-glycoprotein in drug excretion. Nephrol. Dial. Transplant. 16:1607-1614 (2001).
D. Laouari, R. Yang, C. Veau, I. Blanke, and G. Friedlander. Two apical multidrug transporters, P-gp and MRP2, are differently altered in chronic renal failure. Am. J. Physiol. 280:F636-F645 (2001).
Z. H. Huang, T. Murakami, A. Okochi, R. Yumoto, J. Nagai, and M. Takano. Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure. Eur. J. Pharmacol. 406:453-460 (2000).
M. Demeule, M. Brossard, and R. Béliveau. Cisplatin induces renal expression of P-glycoprotein and canalicular multispecific organic anion transporter. Am. J. Physiol. 277:F832-F840 (1999).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yamaguchi, H., Yano, I., Saito, H. et al. Effect of Cisplatin-Induced Acute Renal Failure on Bioavailability and Intestinal Secretion of Quinolone Antibacterial Drugs in Rats. Pharm Res 21, 330–338 (2004). https://doi.org/10.1023/B:PHAM.0000016247.44589.f1
Issue Date:
DOI: https://doi.org/10.1023/B:PHAM.0000016247.44589.f1