Table 4 Estimated pharmacokinetic parameters of sorafenib with or without RT9Gy in rats after (I) treatment with sorafenib alone (40 mg/kg, p.o.) and (II) pretreatment with cyclosporin A (CsA, a P-glycoprotein [P-gp] inhibitor, 20 mg/kg, i.p., 30 min before RT).

From: Robust combination of liver stereotactic body radiotherapy modulates pharmacokinetics of sorafenib toward preferable parameters

PK parameters

Sorafenib (40 mg/kg) only

RT9Gy

CsA (20 mg/kg, i.p.) + sorafenib (40 mg/kg)

CsA (20 mg/kg) i.p.+ RT9Gy

After 1 hr + sorafenib (40 mg/kg)

After 24 hr + sorafenib (40 mg/kg)

After 1 hr + sorafenib (40 mg/kg)

After 24 hr + Sorafenib (40 mg/kg)

AUC0-T (min*µg/mL)

719.5 ± 348.6

1891.0 ± 1151.6a

1456.5 ± 534.4b

784.5 ± 456.7

604.0 ± 421.3c,e

772.4 ± 449.5d,f

Tmax (min)

225 ± 16

195 ± 35

185 ± 40

240 ± 0

200 ± 56

235 ± 12

Cmax (µg/mL)

4.39 ± 2.28

12.26 ± 6.30

8.686 ± 2.73

4.69 ± 2.31

3.74 ± 2.17

5.43 ± 3.22

  1. The data are expressed as the mean ± SEM values (n = 6). AUC, area under the concentration vs. time curve; Tmax, the time at which Cmax is observed; Cmax, peak plasma concentration of the drug after administration.
  2. aRT9Gy + sorafenib (40 mg/kg, p.o.) 1 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.038.
  3. bRT9Gy + sorafenib (40 mg/kg, p.o.) 24 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.018.
  4. cCsA (20 mg/kg, i.p.) + RT9Gy + sorafenib (40 mg/kg, p.o.) 1 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.616.
  5. dCsA (20 mg/kg, i.p.) + RT9Gy + sorafenib (40 mg/kg, p.o.) 24 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.825.
  6. eCsA (20 mg/kg, i.p.) + RT9Gy + sorafenib (40 mg/kg, p.o.) 1 hr later vs. RT9Gy + sorafenib (40 mg/kg, p.o.) 1 hr later, p = 0.028.
  7. fCsA (20 mg/kg, i.p.) + RT9Gy + sorafenib (40 mg/kg, p.o.) 24 hr later vs. RT9Gy + sorafenib (40 mg/kg, p.o.) 24 hr later, p = 0.037.
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