TABLE 2

Plasma pharmacokinetic parameters of ximelagatran and its three metabolites in the VP, VH, and VF following enteral administration of 200 mg of ximelagatran alone (TI; n = 6 pigs) or in combination with 250 mg of erythromycin (TII; n = 6 pigs) Tmax is shown as median and range. All the other values are presented as mean and S.D.

Ximelagatran
OH-melagatran
Ethylmelagatran
Melagatran
TI
TII
TI
TII
TI
TII
TI
TII
AUC0–6 h (h · μM)
   VP 2.28 ± 0.66 1.88 ± 0.94 7.34 ± 2.22 6.17 ± 1.15 0.54 ± 0.19 0.88 ± 0.98 7.15 ± 1.23 10.3 ± 2.86*
   VH 1.17 ± 0.33 1.03 ± 0.51 5.09 ± 2.03 4.38 ± 1.28 0.37 ± 0.16 0.99 ± 1.28 6.88 ± 1.06 9.78 ± 2.68*
   VF 0.91 ± 0.26 0.85 ± 0.38 4.27 ± 1.55 3.76 ± 0.72 0.51 ± 0.15 0.86 ± 0.95 6.30 ± 1.03 9.17 ± 2.52*
AUC0-∞ (h · μM)
   VP 2.28 ± 0.66 1.85 ± 0.98 11.6 ± 9.36 6.39 ± 1.20 0.58 ± 0.19 0.93 ± 1.01 9.33 ± 1.50 12.3 ± 3.62
   VH 1.17 ± 0.33 1.06 ± 0.50 6.91 ± 4.13 4.76 ± 1.24 0.40 ± 0.16 1.00 ± 1.33 9.09 ± 1.59 12.0 ± 3.27
   VF 0.91 ± 0.26 0.86 ± 0.37 4.71 ± 1.95 3.90 ± 0.71 0.56 ± 0.16 0.94 ± 0.98 8.27 ± 1.49 11.1 ± 3.20
Cmax (μM)
   VP 3.12 ± 1.43 2.11 ± 1.33 3.99 ± 1.90 4.08 ± 1.60 0.33 ± 0.18 0.41 ± 0.39 2.22 ± 0.64 3.20 ± 1.03
   VH 1.63 ± 0.68 1.09 ± 0.47 2.64 ± 0.86 3.03 ± 1.45 0.26 ± 0.16 0.46 ± 0.54 2.10 ± 0.54 3.02 ± 0.94
   VF 1.23 ± 0.53 0.86 ± 0.32 2.02 ± 0.70 2.35 ± 0.87 0.26 ± 0.13 0.37 ± 0.36 1.81 ± 0.41 2.75 ± 0.86*
Tmax (h)
   VP 0.2 (0.2–0.5) 0.5 (0.2–0.8) 0.7 (0.5–1.5) 0.7 (0.5–1.5) 0.5 (0.5–1.5) 0.8 (0.5–1.5) 1.3 (1.2–2.2) 1.9 (1.2–2.5)
   VH 0.2 (0.2–0.5) 0.5 (0.2–1.2) 0.9 (0.5–1.9) 0.7 (0.5–1.5) 0.5 (0.5–1.5) 0.9 (0.5–1.5) 1.5 (1.2–2.2) 1.9 (1.2–2.5)
   VF 0.2 (0.2–0.5) 0.5 (0.2–0.9) 0.9 (0.5–1.9) 0.9 (0.5–1.5) 0.9 (0.5–1.8) 0.9 (0.5–1.9) 1.7 (1.2–2.2) 2.1 (1.2–2.5)
t1/2 (h)
   VP 0.2 ± 0.1 0.3 ± 0.1 1.7 ± 0.7 1.7 ± 0.6 2.0 ± 0.3 1.3 ± 0.5* 2.5 ± 1.0 2.0 ± 0.5
   VH 0.2 ± 0.1 0.4 ± 0.1* 1.7 ± 0.6 1.3 ± 0.3 1.8 ± 0.9 1.3 ± 0.6 2.5 ± 1.2 1.9 ± 0.3
   VF
0.2 ± 0.1
0.4 ± 0.1*
1.4 ± 0.4
1.2 ± 0.3
1.9 ± 0.3
1.4 ± 0.4
2.5 ± 1.1
1.9 ± 1.1

  • ↵* p < 0.05