Basic concepts of pharmacokinetics
The disposition of a drug includes the following processes:
• absorption
• distribution
• metabolism
• excretion.
The processes of metabolism and excretion are often referred to as elimination because they function together to eliminate poisons from the body. Pharmacokinetics describes the time course of the blood and tissue concentration profile, while pharmacodynamics refers to the relationship between dose and the intended pharmacological response. The absorption phase relates to the entry of drug from the absorption site. This may be relatively slow, as from the gastrointestinal tract for oral absorption, or rapid if given intravenously.
During the absorption phase, drugs are distributed by the blood to all parts of the body. The uptake of drug into tissues is a time-dependent process and differs between tissues and from drug to drug. Shortly after entry into the tissues, drugs are subject to both metabolism and excretion from the body. These two processes are often the more important for toxicologists and are also often the most variable. Most drugs given intravenously or orally produce blood (or plasma) concentration–time curves of the type shown in Figures 1A and 1B, respectively. Following intravenous admin istration, there is initially a rapid decrease in plasma drug concentration. Decline of plasma drug concentration is usually exponential. For some drugs, it is possible to distinguish two components (biexponential) following intra venous administration: the early phase (a-phase) in which distribution is the major process, and a second period with a slower decay, in which elimination predominates (b-phase). After oral administration, plasma concentrations initially increase while the drug is being absorbed and then decrease when elimination becomes the major process. The drug distribution phase is often not considered, since it tends to be more rapid than either the absorptive or elimination phases; however, in some situations it needs to be considered.
Figure 1 Typical semilogarithmic plots of plasma concentration (C) versus time for a drug given (A) by intra venous injection and (B) orally. The terminal rate of decline of plasma concentration is the same irrespective of the route of administration.
