Article Figures & Data
Figures
- Fig. 1.
Inhibition of the phosphorylation of EGFR in the Geo tumor xenograft following a single i.p. injection of cetuximab at 0.04 and 0.25 mg. Tumors were surgically removed, immediately snap-frozen in liquid nitrogen and stored at −80°C until Western analysis.
- Fig. 2.
A and B, pharmacodynamics of cetuximab in the Geo tumor-bearing mice following a single i.p. administration at 0.25 and 0.04 mg. Nude mice bearing human Geo tumor following a single i.p. administration at dose levels of 0.25 and 0.04 mg. Tumors were surgically removed at 0, 1, 3, 6, 24, 48, and 72 hours and immediately frozen in liquid nitrogen and stored at −80°C until Western analysis. The inhibition of the activated EGFR was quantitated by an ELISA assay. Points, means; bars, ±SD. Pharmacokinetic data were quoted from our previous publication (23).
- Fig. 3.
Inhibition of the phosphorylation of MAPK (A) and Ki-67 expression (B) in the Geo tumor xenograft following a single i.p. injection of cetuximab at 0.25 or 0.04 mg. Tumors were surgically removed, immediately fixed in 10% neutral formalin, embedded in paraffin and analyzed immunohistochemically.
- Fig. 4.
Pharmacokinetic modeling of cetuximab in mice following a single i.v. (A) or i.p. (B) injection at 1, 0.25, and 0.04 mg. The pharmacokinetic data were simultaneously fitted using a one-compartment model. The estimated disposition variables were then linked with the pharmacodynamic model.
- Fig. 5.
Pharmacokinetic and pharmacodynamic modeling of cetuximab in Geo tumor-bearing mice following a single i.p. injection at 0.25 and 0.04 mg. The pharmacokinetic data were simultaneously fitted using a one-compartment model with first-order absorption kinetics. The estimated pharmacokinetic variables were then used to link with the pharmacodynamic model. The pharmacodynamic data were simultaneously fitted using an indirect pharmacodynamic model with an assumption that the phosphorylated EGFR level was assumed to be at steady state in the absence of cetuximab. Also, the reduction of the phosphorylated EGFR measured in the experiment was primarily due to the inhibition by drug.
- Fig. 6.
Simulation of plasma levels of cetuximab in mice with a dosing schedule of q3dx5 at 0.25 and 0.04 mg. The pharmacokinetic data were simultaneously fitted using a one-compartment model with first-order absorption kinetics. The plasma profile was simulated based on an assumption of linear pharmacokinetics for cetuximab with multiple administrations at dose range of 0.25 to 0.04 mg. (•) 0.25 mg, (○) 0.04 mg.
Volume 11, Issue 15
