Pharmacokinetics conceptual parameters

Bioavailability is the other important conceptual pharmacokinetic parameter, in addition to clearance. The key concepts are summarised in Box 5.3. Bioavailability is defined as the proportion of an administered dose that reaches the systemic circulation. It has no units and is... 

Conceptual models of percutaneous absorption which are rigidly adherent to general solutions of Pick s equation are not always applicable to in vivo conditions, primarily because such models may not always be physiologically relevant. Linear kinetic models describing percutaneous absorption in terms of mathematical compartments that have approximate physical or anatomical correlates have been proposed. In these models, the various relevant events, including cutaneous metabolism, considered to be important in the overall process of skin absorption are characterized by first-order rate constants. The rate constants associated with diffusional events in the skin are assumed to be proportional to mass transfer parameters. Constants associated with the systemic distribution and elimination processes are estimated from pharmacokinetic parameters derived from plasma concentration-time profiles obtained following intravenous administration of the penetrant. 

Volume of distribution is a conceptual pharmacokinetic parameter that scales the extent of a drug distributed into the tissues. A well-known parameter, elimination half-life, can be derived from clearance and volume of distribution. It is a very important developability criterion that warrants the desired dose regimen. It should be noted here that half-life must be discussed in the context of a biologically relevant concentration. A purely mathematically derived half-life is sometimes biological irrelevant. Some more definitive explanations and comprehensive discussion of the major pharmacokinetic parameters and their biological relevance have been extensively reviewed.25,26 These parameters should be examined across several different preclinical species to predict the behavior in humans. The DMPK topics will be discussed in Chapters 5 and 6. 

Bioavailability is the other important conceptual pharmacokinetic parameter, in addition to clearance. The key concepts are summarised in Box 5.3. Bioavailability is defined as the proportion of an administered dose that reaches the systemic circulation . It has no units and is usually expressed as a percentage. Values range from 0 to 100%, and will be 100% or complete for an intravenously administered drug. After oral administration, only a proportion of the drug may reach the systemic circulation because of incomplete absorption or because absorbed drug may be metabolised in the gut wall or liver (first-pass metabolism). For... 

This chapter focuses on the conceptual approach to pharmacokinetics, its use as a tool in therapeutics, and in defining drug disposition. The more common mathematical modeling-exponential equation-data analysis approach to pharmacokinetics will not be discussed here. These mathematical techniques are necessary to determine the important pharmacokinetic parameters that are to be discussed however, for medicinal chemists who need to... 

---