Pharmacokinetic Models for Anticancer and Antiviral Drugs Following Administration as Novel Drug Delivery Systems
Physiologically-based pharmacokinetic (PB-PK) models are a valuable means to evaluate drug distribution in tissues. PB-PK models, with its origins in chemical engineering , provide a unified and comprehensive account of drug transport by utilization of differential mass balance equations. The equations and associated parameters, such as organ blood flows and tissue to blood partition coefficients, yield a framework to represent mechanistic information on drug transport. PB-PK models offer advantages of providing predicted tissue drug concentrations as a function of time for different experimental conditions, and by model scale-up for humans. PB-PK models are distinct from other pharmacokinetic data analysis methods in being able to predict individual tissue drug concentrations, and to investigate alterations in physiological parameters on drug disposition. The advantages of PB-PK modeling are counterbalanced by variable parameter estimation methods, lack of uniform model discrimination methods and requirement of large data bases for either model development or validation.
KeywordsMass Transfer Coefficient Pharmacokinetic Model Organ Blood Flow Release Rate Constant Physiological Pharmacokinetic Model
Unable to display preview. Download preview PDF.
- 1.K. B. Bischoff and R. G. Brown. Drug distribution in mammals. Chem. Eng. Prog. 62:33–45 (1966).Google Scholar
- 7.J. M. Gallo, F. C. Lam, and D. G. Perrier. Moment method for the estimation of mass transfer coefficients for physiological pharmacokinetic models. Biopharm. Drug Dispos, (in press).Google Scholar
- 8.J.M. Weissbrod. Comprehensive approach to whole body pharmacokinetics in mammalian systems: Applications to methotrexate, streptozotocin, and zinc. D. Engin. Sci. Thesis, Columbia University, New York, 1979.Google Scholar
- 11.J. M. Gallo, L. L. Chueng, H. J. Kim, J. V. Bruckner, and W. R. Gillespie. Physiological pharmacokinetic models for carbon tetrachloride: Use of oral absorption input functions obtained by deconvolution. Submitted for publication.Google Scholar