The relative distribution of cardiac output among organ vascular beds determines the speed at which organs are exposed to drug. The highly perfused core circulatory components (the brain, lungs, heart, and kidneys) receive the highest relative distribution of cardiac output and therefore are the initial organs to reach equilibrium with plasma drug concentrations. Drug transfer to the less well-perfused, intermediate-volume muscle tissue may take hours to approach equilibrium, and drug transfer to the poorly perfused, large cellular volumes of adipose tissue does not equilibrate for days.

1. Redistribution
   1. As soon as the concentration of drug in the brain tissue is higher than the plasma concentration of drug, a reversal of the drug concentration gradient takes place so that the lipophilic drug readily diffuses back into the blood and is redistributed to the other tissues that are still taking up drug.
   2. Although single, moderate doses of highly lipophilic drugs have very short central nervous system (CNS) durations of action because of redistribution of drug from the CNS to the blood and other less well-perfused tissues, repeated injections of a drug allow the rapid establishment of significant peripheral tissue concentrations.

Basic Principles of Clinical Pharmacology

1. Pharmacokinetic Principles: Drug Absorption and Routes of Administration
2. Drug Distribution
3. Drug Elimination
4. Pharmacokinetic Models
5. Compartmental Pharmacokinetic Models
6. Pharmacodynamic Principles
7. Drug–Receptor Interactions
8. Drug Interactions
9. Clinical Applications of Pharmacokinetic and Pharmacodynamics to the Administration of IV Anesthetics