When drugs are administered, they mix with body tissues and are immediately diluted from the concentrated injectate in the syringe to the more dilute concentration measured in the plasma or tissue. This initial distribution (within 1 minute) after bolus injection is considered mixing within the “central compartment” (Fig. 2-5).

It may take hours or even days for the drug to fully mix with all bodily tissues because some tissues have very low perfusion.

Many anesthetic drugs are highly fat soluble and poorly soluble in water.

1. High fat solubility means that the molecule will have a large volume of distribution because it will be preferentially taken up by fat, diluting the concentration in the plasma.

2. The extreme example of this is propofol, which is almost inseparable from fat.

Following bolus injection, drug primarily goes to the tissues that receive the bulk of arterial blood flow: the brain, heart, kidneys, and liver. These tissues are often called the vessel rich group.

1. The rapid blood flow ensures that the concentration in these highly perfused tissues rises rapidly to equilibrate with arterial blood.

2. For highly fat-soluble drugs, the capacity of the fat to hold the drug greatly exceeds the capacity of highly perfused tissues.

   1. With time (initially, the fat compartment is almost invisible because fat blood flow is low), the fat gradually absorbs more and more drug, sequestering it away from the highly perfused tissues.

   2. This redistribution of drug from the highly perfused tissue to the fat accounts for a substantial part of the offset of drug effect following a bolus of an intravenous anesthetic or fat-soluble opioid (fentanyl).