ABSTRACT
This chapter describes the use of numerical methods in simple and complex enzyme kinetics, compartmental- and physiologically-based pharmacokinetic (PK) models, and PK- pharmacodynamics (PD). It discusses the flexibility allowed by the numerical method to incorporate various mechanistic complexities into a model and to combine various enzyme kinetics, PK, and PD models. Numerical methods provide a flexible and powerful approach to model drug metabolism processes. Rate and integrated equations remain useful and provide clear and useful relationships for model components. In pharmacokinetic compartmental modeling, concentration as a function of time profiles, C(t), are commonly described by multi-exponential functions. Overlapping drug metabolism pathways are the most common mechanism for drug-drug interactions. ordinary differential equations (ODEs) can be easily written for most time-dependent biological processes in drug metabolism and pharmacokinetics. Computational software packages allow for the solution of complex systems directly from the ODEs.
