Drug Distribution Following Parenteral Administration

The blood transports the drug to the tissues, however the drug concentration in the tissues is usually not equal to that in the blood. A number of factors influence the drug concentration in tissues, one of the most important being the blood flow per unit mass of the tissue. Tissues can be broadly classified as poorly-perfused, adequately perfused and well-perfused on this basis as shown in Table 2.1. Note how organs with a relatively small mass, such as the heart and brain, only require a modest blood flow to perfuse them well. The blood flow to the heart musculature (not to be confused with the flow through the heart) is equal to that through the adipose tissue, but the heart has a much smaller mass and so is correspondingly better perfused.

The blood flow controls the rate at which the drug is supplied to the particular tissue, and will be reflected in the drug concentration profile in that tissue. If the tissue is well-perfused, the tissue pharmacokinetics will reach a maximum value at a similar time to that in the blood. However, if the tissue is less well perfused, the supply of drug to the tissue will be rate-limiting and so the concentration in the tissue will increasingly lag behind that in the blood, as shown in Figure 2.6.

The second important factor determining the tissue pharmacokinetics is the affinity of the tissue for the drug. This can take 2 forms; passive or active. Passive affinity is simply the partitioning of the drug. For example, the partitioning of a lipophilic drug into adipose tissues results in high drug concentrations in that tissue, although this is achieved slowly due to the poor perfusion of the adipose tissue.

Table 2.1 Blood flow through various human organs

Table 2.1 Blood flow through various human organs

Drug in Blood

Well Perfused

Poorly Perfused

Adequately Perfused

Figure 2.6. Pharmacokinetic profiles of drugs in tissues of varying perfusion. Solid line: concentration in blood; dotted line: concentration in tissue

Active affinity occurs if the drug is taken up by the tissue by a specific transport mechanism. An example of this is guanethidine, which is used in the treatment of hypertension. This drug reaches its site of action by active transport into the heart and skeletal muscle. As a result the drug concentrations in these tissues are much higher than would be expected on the basis of partition from the blood, and due to the affinity of the tissue for the drug, are sustained for a much longer period than those in the bloodstream (Figure 2.7).

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