Chapter 16 - Multicompartment model

Abstract

This chapter offers an in-depth analysis of the intricate dynamics of drug distribution within the body using pharmacokinetic equations, tables, and graphs. It commences with an introduction to multicompartment models, elucidating their critical role in comprehending how drugs distribute to tissues. It discusses the specifics of two-compartmental modeling following intravenous (IV) bolus administration. This section provides a detailed explanation of the determination of hybrid and micro constants, which are essential for understanding the pharmacokinetics of drug distribution and elimination. It further explores the method of residuals, also known as the Feathering Technique or Curve Stripping. This technique is instrumental in determining micro constants, which are pivotal in understanding the rate at which the drug moves between compartments. The subsequent sections delve into the estimation of pharmacokinetic parameters and the application of two-compartment models following IV infusion and extravascular administration. These sections provide a comprehensive understanding of how drugs distribute and eliminate in the body under different administration methods. The chapter then extends the discussion to three-compartment models with IV bolus injection and multiple dosing regimens. It provides meticulous calculations for loading and maintenance doses, offering readers a practical understanding of dosage regimen design. Discussions on the extent of accumulation and the kinetics of multiple oral dosing are included, providing insights into how repeated dosing affects drug accumulation in the body. The clinical significance of these models, emphasizing their importance in dosage regimen design and the extent of drug accumulation, providing insights into how drug accumulation can affect therapeutic outcomes are also provided. Two appendices cover the basics of compartment modeling and Laplace transformation. These provide readers with the necessary mathematical background to understand the pharmacokinetic models discussed in this chapter.