Article Figures & Data
Figures
- Figure 1.
Tumor volume (A) and weight (B) changes in BALB/c mice: negative control (•), p.o. DHP107 at 50 mg/kg (▪), and i.v. Taxol at 10 mg/kg (○; n = 13–14). EMT-6 murine mammary tumor cells (1 × 104) were implanted s.c. (day 0). Drugs were administered daily for three 5-day cycles separated by 2-day intervals.
- Figure 2.
Distribution of paclitaxel in blood and major tissues. A, paclitaxel concentrations in blood and various tissues were analyzed at several time points after p.o. administration of DHP107 at 50 mg/kg (○) and i.v. Taxol at 10 mg/kg (•) in female BALB/c mice. B, immunohistochemistry with the antitaxane antibody showed paclitaxel localization in tissues 2 h after p.o. administration of DHP107 (50 mg/kg).
- Figure 3.
Intraluminal kinetics of DHP107. A, the tissue and fluid concentrations of paclitaxel were determined at several points after p.o. administration of 50 mg/kg DHP107 (○) and i.v. Taxol at 10 mg/kg (•) in female BALB/c mice. B, immunohistochemistry of paclitaxel in intestinal tract tissues 2 h after p.o. DHP107 administration (50 mg/kg).
- Figure 4.
Fate of DHP107 in artificial intestinal fluid with or without bile salts in vitro (top) and in intestinal lumen at various times after p.o. administration of 50 mg/kg DHP107 containing Sudan IV (bottom).
- Figure 5.
Accumulation of lipid in jejunum tissue after p.o. administration of 50 mg/kg DHP107 (A). Intestinal segments were fixed in paraformaldehyde and embedded in OCT. Frozen sections were stained with lipid-specific Oil Red O and with hematoxylin, and visualized by light microscopy. Lipid absorption in the intestine after p.o. administration of 50 mg/kg DHP107 (B). Intestinal absorptive cells for negative control and oral DHP107 group, 0.5 h after p.o. administration, were observed with transmission electron microscopy. Arrows, lipid bodies in the cytosol.
Tables
- Table 1.
Calculated AUC0–24 of paclitaxel in blood and tissues (n = 3) after p.o. administration of 50 mg/kg DHP107 and i.v. administration of 10 mg/kg Taxol
DHP107 (50 mg/kg) Taxol (10 mg/kg) Bioavailability in organs (%) Tmax (h) Cmax (μg/mL) AUC0–24 (μg·h/g) Tmax (h) Cmax (μg/mL) AUC0–24 (μg·h/mL) Blood 2 2.2 ± 0.1* 10.4 ± 2.4 — 23.2 ± 3.1 9.1 ± 1.1 23 Liver 2 63.5 ± 11.8 363.7 ± 80.0 — 50.0 ± 2.8 67.6 ± 7.4 108 Spleen 4 7.7 ± 0.8 56.5 ± 6.2 0.5 1.7 ± 0.2 1.2 ± 0.3 942 Kidney 2 13.1 ± 2.7 83.0 ± 13.6 — 33.7 ± 1.2 23.6 ± 1.5 070 Heart 2 5.3 ± 1.3 36.4 ± 5.6 — 10.3 ± 1.7 7.7 ± 1.1 95 Lung 2 12.2 ± 3.8 69.4 ± 17.4 — 19.9 ± 2.5 30.8 ± 5.1 45 Stomach 0.5 2,637.1 ± 224.6 11,978.9 ± 2,296.2 0.5 3.2 ± 0.6 6.2 ± 1.1 38,642 Jejunum 2 78.4 ± 17.0 617.8 ± 102.0 0.5 10.6 ± 1.2 21.9 ± 3.6 564 Ileum 8 112.7 ± 31.9 1,543.6 ± 392.7 1 5.5 ± 2.0 20.2 ± 4.3 1,528 Colon 24 113.1† 2,097.4 ± 145.4 2 2.6 ± 0.3 16.1 ± 1.9 2,605
Volume 6, Issue 12
