Table 3 Estimated pharmacokinetic parameters of sorafenib with or without RT2Gy 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 parameter

Sorafenib (40 mg/kg) only

RT2Gy

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

CsA (20 mg/kg) i.p.+ RT2Gy

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

1669.0 ± 958.7a

296.9 ± 169.8b

784.5 ± 456.7

277.7 ± 182.9c,e

1113.3 ± 608.0d,f

Tmax (min)

225 ± 16

175 ± 40

204 ± 25

240 ± 0

198 ± 66

225 ± 30

Cmax (µg/mL)

4.39 ± 2.28

10.14 ± 5.93

1.89 ± 1.08

4.69 ± 2.31

1.72 ± 0.96

7.71 ± 3.41

  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. aRT2Gy + sorafenib (40 mg/kg, p.o.) 1 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.046.
  3. bRT2Gy + sorafenib (40 mg/kg, p.o.) 24 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.036.
  4. cCsA (20 mg/kg, i.p.) + RT2Gy + sorafenib (40 mg/kg, p.o.) 1 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.032.
  5. dCsA (20 mg/kg, i.p.) + RT2Gy + sorafenib (40 mg/kg, p.o.) 24 hr later vs. sham RT + sorafenib (40 mg/kg), p = 0.224.
  6. eCsA (20 mg/kg, i.p.) + RT2Gy + sorafenib (40 mg/kg, p.o.) 1 hr later vs. RT2Gy + sorafenib (40 mg/kg, p.o.) 1 hr later, p = 0.011.
  7. fCsA (20 mg/kg, i.p.) + RT2Gy + sorafenib (40 mg/kg, p.o.) 24 hr later vs. RT2Gy + sorafenib (40 mg/kg, p.o.) 24 hr later, p = 0.023.
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