Table 5.

Pharmacokinetic variables of gemcitabine and dFdU after 1,000 mg/m2 i.v. doses of gemcitabine alone (day 1, cycle 1) and in combination (day 15, cycle 1) with sorafenib after 100, 200, and 400 mg bid doses of sorafenib (geometric mean, % CV)

Dose of sorafenib (mg)nCmax (mg/L)
AUC0-tn (mg·h/L)*
Gemcitabine aloneGemcitabine plus sorafenibRatio (90% CI) gemcitabine plus sorafenib vs gemcitabine aloneGemcitabine aloneGemcitabine plus sorafenibRatio (90% CI) gemcitabine plus sorafenib vs gemcitabine alone
Gemcitabine
    100 bid210.6 (34%)9.40 (76%)0.87
    200 bid412.4 (38%)14.7 (42%)1.19
    400 bid (50 mg tablet)75.0 (502%)11.8 (203%)2.46
    400 bid (200 mg tablet)47.0 (57%)8.0 (123%)1.41
    400 bid (pancreatic cancer cohort)610.5 (25%)3.6 (125%)0.69§
dFdU
    100 bid227.5 (12%)29.0 (8%)1.05195.0 (26%)162 (6%)0.83
    200 bid436.5 (12%)36.7 (23%)1.01163.0 (28%)163.0 (17%)1.00
    400 bid (200 mg tablet)739.0 (24%)39.1 (27%)1.05222.3 (27%)197.6 (35%)0.93
    400 bid (pancreatic cancer cohort)443.3 (36%)38.3 (31%)1.10225.0 (18%)164.1 (24%)0.91
    400 bid (pancreatic cancer cohort)1042.8 (20%)41.2 (42%)1.13163.4 (24%)124.6 (21%)0.86
  • * AUC0-tn: area under the plasma concentration versus time curve from time 0 to last data point; gemcitabine AUC values were not determined due to insufficient plasma concentration data.

  • The ratio is the geometric least-square mean ratio.

  • n = 5.

  • § n = 3.