Table 2.

Comparison of the effects of the crystal form and solid dispersion preparations of KRN633 on A549 tumor-bearing athymic rats

Dose (mg/kg)Solid dispersion treated
Crystal form treated
TGI%Regression (%)Weight loss (%)*Total urinary protein (mg/dL)AUC (μg h/mL)TGI%Regression (%)AUC (μg h/mL)
Vehicle2.9
0.119.46.0
0.321.95.2
182.12.65.114
29.6
3>10019.34.5
533.92.3
10>10034.813.833.775.2
2060.66.5
30>10045.610.7 (d 14)57.9
5081.1§
100>10042.820.8 (d 18)ND76.6>1003.79.4
  • NOTE: The effects of the crystal form and solid dispersion preparations were evaluated by separate experiments. A549 human lung carcinoma tumors were established after the s.c. implantation of tumor cells into the flank of athymic rats. After randomization, daily oral administration of the crystal form or solid dispersion preparations was initiated and continued for 2 weeks (n = 5). The average initial tumor volumes (day 0) of the rat groups used to evaluate the efficacy of the crystal form and solid dispersion preparations were 162 and 231 mm3, respectively. The TGI% induced by the solid dispersion and crystal form preparations was determined at days 14 and 12, respectively. On days 13 and 14, each rat was placed in a metabolic cage and its urine was collected over 24 hours.

  • * Amount of maximum weight reduction from the initial weight at day 0 during the study (the corresponding day is indicated in brackets; losses that are >1% of the initial weight are shown). AUCwas derived from the serum concentrations of KRN633 after a single oral administration at each dose in athymic rats.

  • P < 0.001 (KRN633-treated groups versus vehicle-treated group).

  • P < 0.01.

  • § P < 0.05.

  • ND, not determined.