[Pharmacokinetics of intravenous non-steroidal anesthetics].

Abstract

Even though the anesthetic agents thiopental, ketamine, propanidid and etomidate all belong to very different chemical families they are all characterized by a very large degree of liposolubility. This explains their rapid penetration into the brain. The pharmacokinetic model of thiopental is a three compartment model. There is strong protein binding and only the free fraction is active. The very short action of the product after a single injection is due to the rapid redistribution of the agent into the muscle mass because its hepatic metabolization is very slow. However, when given over prolonged time the adipose compartment plays an important role in the mixture of the product, explaining the prolonged sleep produced. The central depressant actions of thiopental and consequently its action on CMRO2 depend on the initial dose and the route of administration. A single and massive injection produces a small and temporary reduction in the CMRO2 even though the plasmic concentration is high. In contrast prolonged intravenous infusion produces more severe and longer lasting depression of the CMRO2. The pharmacokinetic model of ketamine is tri-compartmental. There is weak protein binding. After IV injection ketamine rapidly enters the brain and the maximum concentration is reached one minute later. After that the cerebral concentration rapidly falls as does the plasma level. Signs of waking are seen at a concentration of 130 micrograms per gram of tissue. An increase in the dose of ketamine does not much influence the duration of analgesia but increase the waking time. This suggests that its indication in ambulatory anesthesia should be looked at with care. It is metabolized by the liver with the formation of several metabolites of which some are active. The kinetics of propanidid can be explained on the basis of a monocompartmental model. The speed of the fall in plasma level of the product is related to the speed of injection. High plasma concentrations mobilize a larger quantity of plasma pseudo-cholinesterases, increasing thus the speed of degradation. The product is rapidly hydrolized (plasma and liver cholinesterases). The duration of action is longer when used at low doses or when it is administered at a constant dose. Propanidid does not have any accumulative effect. The kinetics of etomidate follow a tri-compartmental model. It is very rapidly and largely distributed in the organism, the peak cerebral concentration being reached in less than one minute. There is strong protein binding. Repeated administration of the drug produces an increase in anesthetic sleep but also a delay in recovery. Etomidate is hydrolized by hepatic esterases.