Integration of in silico and in vitro platforms for pharmacokinetic-pharmacodynamic modeling.
BACKGROUND
Pharmacokinetic-pharmacodynamic (PK-PD) modeling enables quantitative prediction of the dose-response relationship. Recent advances in microscale technology enabled researchers to create in vitro systems that mimic biological systems more closely. Combination of mathematical modeling and microscale technology offers the possibility of faster, cheaper and more accurate prediction of the drug's effect with a reduced need for animal or human subjects.


METHODS
This article discusses combining in vitro microscale systems and PK-PD models for improved prediction of drug's efficacy and toxicity. First, we describe the concept of PK-PD modeling and its applications. Different classes of PK-PD models are described. Microscale technology offers an opportunity for building physical systems that mimic PK-PD models. Recent progress in this approach during the last decade is summarized.


RESULTS
This article is intended to review how microscale technology combined with cell cultures, also known as 'cells-on-a-chip', can confer a novel aspect to current PK-PD modeling. Readers will gain a comprehensive knowledge of PK-PD modeling and 'cells-on-a-chip' technology, with the prospect of how they may be combined for synergistic effect.


CONCLUSIONS
The combination of microscale technology and PK-PD modeling should contribute to the development of a novel in vitro/in silico platform for more physiologically-realistic drug screening.
Sung
Jong Hwan
JH
Cornell University, Chemical and Biomolecular Engineering, Ithaca, NY 14850, USA.
Esch
Mandy B
MB
Shuler
Michael L
ML
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D046210:Microfluidic Analytical Techniques; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D000069437:Pharmacological Phenomena; D051381:Rats; D012107:Research Design
D004364:Pharmaceutical Preparations