[Absorption, distribution, metabolism and excretion of T-3761, a new quinolone derivative, in experimental animals]

Abstract

We studied the absorption, distribution, metabolism and excretion of T-3761, a new quinolone derivative, in experimental animals. The following results were obtained. 1. The peak serum levels of T-3761 after a single oral administration to various fasting animals at a dose of 5 mg/kg were high in the order of rats, dogs, mice and rabbits, showing favorable absorption in all animals except for rabbits. In mice and rats, T-3761 showed higher peak serum levels than ofloxacin and ciprofloxacin but T-3761 were more rapidly eliminated from serum than ofloxacin and ciprofloxacin. 2. Tissue concentrations of T-3761 in rats were similar to those of ofloxacin but its ratio of tissue to serum levels were lower than those of ofloxacin. 3. Urinary excretion of T-3761 as active form until 24 hours after oral administration was 27.3%, 63.1%, 41.0% and 63.3% in mice, rats, rabbits and dogs, respectively. Only unchanged T-3761 was detected as active form in urine of all animals tested. In rats, urinary concentrations until 2 hours after administration were higher than those of ofloxacin. 4. Biliary excretion of T-3761 in mice and rats were 2.9% and 1.4% as active form. 5. The absorption of T-3761 was not different in male and female rats or 8 and 14 weeks old rats. The meal lowered absorption of T-3761 in rats. There was no significant difference in serum levels, urinary excretion and distribution to tissues after multiple administration of T-3761 comparing with its single administration. 6. In rats with liver dysfunction induced by D-galactosamine, the serum levels and urinary excretion were slightly higher than in normal rats. On the other hands, in rats with kidney dysfunction induced by HgCl2, the serum levels were significantly higher and urinary excretion of T-3761 was significantly lower than in normal rats. Above results show that T-3761 has unique characteristics in absorption, excretion and distribution after oral administration to animals among new quinolones, i.e., T-3761 was eliminated rapidly and poorly distributed to tissues but showed superior absorption and high peak serum levels.