Differences in the hepatobiliary transport of two quinolone antibiotics, grepafloxacin and lomefloxacin, in the rat

Hiroyuki Sasabe, Yukio Kato, Tetsuya Terasaki, Akira Tsuji, Yuichi Sugiyama

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

The biliary excretion of grepafloxacin (GPFX) was compared with that of lomefloxacin (LFLX) in rats. The biliary clearances (Cl(plasma)(bile)) of GPFX was 2.9 times greater than LFLX based on the plasma concentration reached during constant intravenous (iv) infusion. The liver-plasma unbound concentration ratio, K(pu), of GPFX (1.7) was also higher than that of LFLX (0.7). The hepatic uptake clearance, assessed from an integration plot analysis, of GPFX was comparable with the hepatic blood flow rate, and 1.5 times that of LFLX, indicating that membrane transport in the uptake process is more efficient for GPFX. This was also supported by the difference between the uptake clearance of GPFX and LFLX in isolated rat hepatocytes. The bile-liver unbound concentration ratio of GPFX and LFLX was approximately 6 and 3, respectively, and the biliary clearance based on the unbound liver concentration of GPFX was 1.8 times that of LFLX. These results suggest that the concentrative transport of GPFX also across the canalicular membrane was more efficient than that of LFLX. Thus, the membrane transport activity via both sinusoidal and canalicular membranes determines the net excretion of each compound.

Original languageEnglish
Pages (from-to)151-158
Number of pages8
JournalBiopharmaceutics and Drug Disposition
Volume20
Issue number3
DOIs
Publication statusPublished - 1999 Mar 30

Keywords

  • Grepafloxacin
  • Hepatobiliary transport
  • Lomefloxacin
  • Quinolone antibiotics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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