Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats.

Article Details

Citation

Yamaguchi H, Yano I, Saito H, Inui K

Effect of cisplatin-induced acute renal failure on bioavailability and intestinal secretion of quinolone antibacterial drugs in rats.

Pharm Res. 2004 Feb;21(2):330-8.

PubMed ID
15032316 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CiprofloxacinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Details
DigoxinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Inducer
Details
GrepafloxacinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details
LevofloxacinP-glycoprotein 1ProteinHumans
Unknown
Substrate
Inhibitor
Details