Drug distribution and elimination in anaesthetic practice

Abstract

An understanding of pharmacokinetics is vital for the practice of anaesthesia. Drugs are, after administration, distributed throughout the body to the effect site (mostly the brain) to exert their effects. This can be influenced by differences in protein binding, systemic blood flow, and concomitant medication. Elimination of drugs from the body is through two main routes: either unchanged through the kidneys or through metabolism by the liver (and consecutive excretion through the kidneys). This process depends on the amount of hepatic blood flow and the amount of hepatic extraction. This in turn depends on the amount of protein binding and the intrinsic hepatic clearance. The cytochrome P450 enzyme family also plays an important role in drug elimination. Individual differences in enzyme activity can lead to differences in drug effect and clearances. Changes in enzyme activity by enzyme induction and inhibition can also be of influence on drug clearance. Compartmental, non-compartmental, and physiologically based models, and various statistical approaches to estimate these models, may be used to analyze the distribution and elimination of anaesthetic agents.