The subacute toxicity and toxicokinetics of a new
fluoroquinolone antibiotic,
DW-224a, were evaluated after single (on the 1st day) and 4-week (on the 28th day)
oral administration of the
drug at doses of 0 (to serve as a control), 10, 30, and 90 mg/kg/d, to male and female dogs (n=3 for male and female dogs for each dose). During the test period, clinical signs, mortality,
body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathology were examined. The 4-week repeated oral dose of
DW-224a resulted in
vomiting, salivation, increased serum
cholesterol level, and
atrophy of thymus and testes. The target organ was determined to be the thymus and testes. The absolute toxic dose of
DW-224a was 30 mg/kg and the level at which no adverse effects were observed was 10 mg/kg for both sexes. There were no significant gender differences in the pharmacokinetic parameters of
DW-224a for each dose after both single and 4-week
oral administration. The pharmacokinetic parameters of
DW-224a were dose independent after a single
oral administration; the time to reach the peak plasma concentration (T(max)) and the dose-normalized area under the plasma concentration-time curve from time zero to 24 h in plasma (AUC(0-24 h)) were not significantly different among the three doses. The accumulation of
DW-224a after 4-week
oral administration was not notable at the toxic dose of 90 mg/kg/d. For example, after 4-week administration, the dose-normalized AUC(0-24 h) value at 90 mg/kg/d (7.69, 7.05 microg h/ml) was not significantly greater than that
at 10 mg/kg/d. After 4-week
oral administration, the dose-normalized C(max) and AUC(0-24 h) at 90 mg/kg/d were not significantly higher and greater, respectively, than those after a single
oral administration.