Limits...
A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens-a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems.

Li X, Qian L, Bittner ML, Dougherty ER - Cancer Inform (2012)

Bottom Line: The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical data in order to decrease costs of drug development and increase pipeline productivity, since it is extremely expensive and difficult to get the optimal compromise of dosage and schedule through empirical testing.The second objective is to provide valuable suggestions to adjust individual drug dosing regimens to improve therapeutic effects considering most anticancer agents have wide inter-individual pharmacokinetic variability and a narrow therapeutic index.It is proved analytically that there exists an optimal drug dosage and interval administration point, and demonstrated through simulation study.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.

ABSTRACT
Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical data in order to decrease costs of drug development and increase pipeline productivity, since it is extremely expensive and difficult to get the optimal compromise of dosage and schedule through empirical testing. The second objective is to provide valuable suggestions to adjust individual drug dosing regimens to improve therapeutic effects considering most anticancer agents have wide inter-individual pharmacokinetic variability and a narrow therapeutic index. A dynamic hybrid systems model is proposed to study drug antitumor effect from the perspective of tumor growth dynamics, specifically the dosing and schedule of the periodic drug intake, and a drug's pharmacokinetics and pharmacodynamics information are linked together in the proposed model using a state-space approach. It is proved analytically that there exists an optimal drug dosage and interval administration point, and demonstrated through simulation study.

No MeSH data available.


Related in: MedlinePlus

τ = 8, ζ = 24, Ψ = −0.24.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3298374&req=5

f6-cin-11-2012-041: τ = 8, ζ = 24, Ψ = −0.24.

Mentions: Figures 5–7 show the responses of tumor under three dosing regimens (all with same total drug intake α = 3.0). The left figure (Fig. 5) corresponds to the small frequent dosing, the right figure (Fig. 7) corresponds to the large infrequent dosing, and the case of intermediate dosing in between (Fig. 6). Other parameter setting for the above figures: β1 = 1.0, β0 = 0.2, k1 = 1.0, θw = 40, , θ̱ = 1.0, θ̄ = 21, and λd = 0.5.


A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens-a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems.

Li X, Qian L, Bittner ML, Dougherty ER - Cancer Inform (2012)

τ = 8, ζ = 24, Ψ = −0.24.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3298374&req=5

f6-cin-11-2012-041: τ = 8, ζ = 24, Ψ = −0.24.
Mentions: Figures 5–7 show the responses of tumor under three dosing regimens (all with same total drug intake α = 3.0). The left figure (Fig. 5) corresponds to the small frequent dosing, the right figure (Fig. 7) corresponds to the large infrequent dosing, and the case of intermediate dosing in between (Fig. 6). Other parameter setting for the above figures: β1 = 1.0, β0 = 0.2, k1 = 1.0, θw = 40, , θ̱ = 1.0, θ̄ = 21, and λd = 0.5.

Bottom Line: The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical data in order to decrease costs of drug development and increase pipeline productivity, since it is extremely expensive and difficult to get the optimal compromise of dosage and schedule through empirical testing.The second objective is to provide valuable suggestions to adjust individual drug dosing regimens to improve therapeutic effects considering most anticancer agents have wide inter-individual pharmacokinetic variability and a narrow therapeutic index.It is proved analytically that there exists an optimal drug dosage and interval administration point, and demonstrated through simulation study.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.

ABSTRACT
Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical data in order to decrease costs of drug development and increase pipeline productivity, since it is extremely expensive and difficult to get the optimal compromise of dosage and schedule through empirical testing. The second objective is to provide valuable suggestions to adjust individual drug dosing regimens to improve therapeutic effects considering most anticancer agents have wide inter-individual pharmacokinetic variability and a narrow therapeutic index. A dynamic hybrid systems model is proposed to study drug antitumor effect from the perspective of tumor growth dynamics, specifically the dosing and schedule of the periodic drug intake, and a drug's pharmacokinetics and pharmacodynamics information are linked together in the proposed model using a state-space approach. It is proved analytically that there exists an optimal drug dosage and interval administration point, and demonstrated through simulation study.

No MeSH data available.


Related in: MedlinePlus