Basic study of regulated factors on the metabolism and biliary transfer of fluoroquinolones

Abstract

Many fluoroquinolones developed in Japan have good biliary transfer, and are put to clinical use for biliary tract infection.However, it is not regulated what kind of fluoroquinolone are suitable for chemotherapy of biliary tract infection.In this study, we examined biliary and urinary concentration of sparfloxacin (SPFX), pazufloxacin (PZFX), and DU-6859a, a new fluoroquinolone, and the rate of un-changed fluoroquinolones and their glucuronides in three kinds of hyperbilirubinemic rats.Where there was obstructive jaundice, each unchanged fluoroquinolone was transferred to bile at a lower rate than the control, but was excreted in the urine at a higher rate than the control.Both PZFX and DU-6859a was transferred to bile at the higher rate than SPFX.In EHBR, the excretion rate of both unchanged fluoro-quinolones and the associated glucuronides into bile decreased remarkably compared with the control, but the excretion rate of the associated glucuronides into urine increased compared with rats with obstructive jaundice, where whole UDP-glucuronic acid levels decreased.In the Gunn rat, each excretion rates into bile varied according to the kind of fluoroquinolone, due to varying affinities for plasma protein.PZFX and DU-6859a, which have a low binding rate to plasma protein, were excreted in bile at a higher level than SPFX.A proportion of fluoroquinolones may be metabolised by different isoenzymes of UDP-glucuronosyltransferase from bilirubin, because there were glucuronides of PZFX and DU-6859a in the bile of Gunn rats.Thus, the use of a fluoroquinolone as an antibacterial agent in patients with biliary tract infection may be affected by the grade of jaundice and level of liver dysfunction in these patients.