Semi-Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for the Combination Use of @entity619 and XXXX in Breast Cancer.

@entity9170 @entity5 @entity38383 @entity619 @entity1726 @entity136
UNASSIGNED: Our study aimed at the investigation of in vivo anticancer effect of the combination use of @entity619 ( @entity9170 ) and @entity136 ( @entity38383 ) as well as the development of pharmacokinetic/pharmacodynamic (PK/ @entity1726 ) models in MCF-7 xenograft model. Further, simulations were conducted to optimize doses and administration schedules. The inhibitory effect of different doses and administration schedules were investigated in MCF-7 xenograft model. Semi-mechanism-based PK/ @entity1726 models were established based on the preclinical data to characterize the relationship between plasma concentration and the time course of the drug response quantitatively. The PK/ @entity1726 models were further applied to predict and optimize doses and administration schedules, which would lead to @entity5 stasis by the end of the treatment. Synergistic effect was observed in the @entity1726 study in vivo and further confirmed by the estimated combination index    obtained from PK/ @entity1726 models. The optimum dose regimen was selected as @entity9170 2 mg/kg, qd and @entity38383 10 mg/kg, q2d based on the simulation results. In summary, the @entity1726 interaction between @entity9170 and @entity38383 was demonstrated as synergism by both experimental results and modeling approach. Dosage regimens were optimized as predicted by modeling and simulations, which would provide reference for preclinical study and translational research as well.    2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:4399-4408, 2015.
