Abstract
Patients treated with DU-6859a developed liver dysfunction more often than patients given any other fluoroquinolone, and the rates of occurrence of liver dysfunction differ according to sex, with males occurrence more common in more than females. The causes of liver dysfunction are thought to be hepatic cell obstruction by DU-6859a, changes in intestinal bacteria as a result of the high antibacterial potency of DU-6859a, increases in cheno-deoxycholic acid in the enterohepatic circulation as a result of blocking conversion of primary bile acids to secondary bile acids, or related to female hormones. Accordingly, to determine whether intestinal bacteria cause the liver dysfunction we administered low and high doses of DU-6859a to germ-free mice, carried out serum biochemistry tests, measured concentrations of bile acids in the gallbladder and bile acid components, and assessed whether that sufferred from liver dysfunction or not. The GOT values of the male mice averaged 598± 158 IU/1 in the controls and 283± 56 IU/1 in the high-dose DU-6859a group, and in female mice, 598±124 IU/1 in the controls and 283±56 IU/1 in high-dose DU-6859a group and the difference between these groups. GPT values in the male mice were 96± 22 IU/1 in the controls and 42± 2 IU/1 in the high-dose DU-6859 group and in the female mice, 177± 45 IU/1 in the controls and 165± 40 IU/1 in the high-dose DU-6859a group. There was no significant differences between these groups, and there were no significant differences between the bile acids in the gallbladder or bile acids components in the four groups. Liver dysfunction caused by DU-6859a proved to be strongly related to intestinal bacteria.
