Table 6

Pharmacokinetic analysis of drug regimens in mice with reference to human studies. Pharmacokinetic (PK) parameters (mean ± SE) based on noncompartmental analysis using WinNonlin (Pharsight Corp.). IP, intraperitoneal; IV, intravenous; PO, orally; G, gavage; qwk, weekly; qd, daily.

DrugSpeciesDoseRouteSchedulePK
data at
AnalyteAUClast
(ng h/ml)
Cmax
(ng/ml)
Tmax
(hours)
Terminal
t1/2
(hours)
Cmin
(ng/ml)
Reference
SirolimusMouse0.5
mg/kg
IPq48h48 hSirolimus4,276 ± 329983 ± 98113.614.9 ± 2.0
TemsirolimusHuman25 mgIVqwkD7 or D28Temsirolimus1,580 ± 270595 ± 1020.512.8(50)*
Sirolimus3,810 ± 2,21066 ± 35148.8
Sum5,860 ± 2,340
EverolimusHuman10 mgPOqdEverolimus514 ± 23161 ± 1713.2 ± 7.2(55)*
Sunitinib
malate
Mouse10
mg/kg
Gq12h12 h (D1)Sunitinib449.8 ± 41.1108.5 ± 5.5224.2 ± 0.1
Desethyl
sunitinib
174.4 ± 24.037.8 ± 0.222.63.0 ± 0.1
Sum624.27.2
Sunitinib
malate
Human50 mgPOqd (D1–28)24 h (D1)Sunitinib420 ± 21027.7 ± 14.15(68)*
Desethyl
sunitinib
63.6 ± 33.74.1 ± 2.25
Sum483.6
Sunitinib
malate
Human50 mgPOqd (D1–28)24 h (D28)Sunitinib1,296 ± 60972.2 ± 31.08.544.0 ± 26.0(68)*
Desethyl
sunitinib
592 ± 39133.7 ± 24.66.518.8 ± 8.5
Sum1,88862.8
ErlotinibMouse12.5
mg/kg
Gq12h12 h (D1)Erlotinib27,042 ± 2,5693,513 ± 27133.1521 ± 169
Desmethyl
erlotinib
3,970 ± 330526 ± 7732.550 ± 23
ErlotinibHuman150 mgPOqd24 h (D1)Erlotinib11,860 ± 5,010872 ± 3993385 ± 213(57)*
Desmethyl
erlotinib
835 ± 47968 ± 453.625 ± 18
ErlotinibHuman150 mgPOqd24 h (D28)Erlotinib43,760 ± 22,5602,528 ± 1,18724.21,473 ± 877(56)*
DovitinibMouse30
mg/kg
Gqd24 h (D1)Dovitinib6,078 ± 710373 ± 14.665.441.2 ± 9.3
DovitinibHuman500 mgPO5 d on/
2 d off
24 h (D1)Dovitinib2,200 – 8,251180 – 487(69)*
DovitinibHuman500 mgPOqd24 h (D1)Dovitinib3,734 ± 2,115223 ± 128(70)*
(D15)Dovitinib4,340 ± 3,775267 ± 17821

*Mean ± SD.