Miloxacin, a novel chemotherapeutic agent, has been reported to have very potent antibacterial activity to E. coli, Klebsiella, Proteus and other Gram-negative rods and be excreted into bile at high levels. Therefore, the effectiveness of
miloxacin against biliary tract
infections and its excretion into bile in patients were investigated. The results were as follows: i) Comparative studies on the excretion of
miloxacin,
nalidixic acid (NA) and
cephalexin (CEX) into bile of patients operated in gallbladder were performed by a crossover method. The maximum concentration of
miloxacin after
oral administration of 500 mg ranged from 18.2 to 24.0 micrograms/ml and were much higher than those of NA (5.3 micrograms/ml) and CEX (3.4 micrograms/ml). The mean recovery of
miloxacin within 6 hours was 0.256% and much greater than those of NA (0.075%) and CEX (0.027%). ii) Into bile, intact
miloxacin and its metabolites (the
glucuronides of
miloxacin and M-2) were excreted but M-1 was scarcely excreted. Regression analysis of the concentrations by the bioassay compared with those intact
miloxacin by the HPLC method gave a good correlation with r = 0.96. iii) The clinical effectiveness against the biliary tract
infections was investigated in 29 cases.
Miloxacin showed the excellent effect in 8 cases and the good effect in 17 cases, giving an effective ratio of 86.2%. Especially, all of the cases dosed with
miloxacin over 34 mg/kg in a day showed excellent or good results. iv) The rates of clinical effectiveness were 85.7, 80.0% and 71.4% in E. coli, Klebsiella and
Proteus infections, respectively. The antibacterial activity of
miloxacin against 27 strains isolated in this test was more potent than those of NA and CEX. v) During the clinical tests, none of any side effect with
miloxacin was observed in both of subjective and objective symptoms. These results show that
miloxacin is expected to be fully applicable on the
therapy of biliary tract
infections.