Читать книгу Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulations - Sheila Annie Peters - Страница 16

The dose and dosing frequency of a drug (dosage regimen), needed to maintain an efficacious concentration at the site of its pharmacological action, for a duration that is long enough to achieve the therapeutic objective, should be safe and convenient to the patient. To achieve this optimal exposure at the target site of pharmacological action in humans, the rate and extent of multiple processes like drug absorption from the site of administration into systemic circulation, tissue distribution, metabolism, and elimination (ADME) are optimized during lead optimization in drug discovery. Pharmacokinetics (PK) is the study of the fate of drug in the body, that determines its exposure/concentration at the target effect site, driven by ADME processes. The relationship of the exposure/concentration at the target effect site to the onset, intensity, and duration of drug action is determined by pharmacodynamics (PD). A well‐defined, quantitative relationship between drug concentrations in biological fluids and pharmacodynamic effect can support the selection of dose and dosing regimen for early clinical trials. This chapter is intended to provide a brief overview of PK and PD principles. The forthcoming chapters will draw heavily upon the concepts laid out in this chapter.