TCI - the pharmacokinetic model

Target Controlled Infusion (TCI) is a logical approach to the development of improved administration techniques for an intravenous anaesthetic agent. TCI is based on an understanding of the agent’s pharmacokinetic properties.
http://www.anesthesia.at/anesthesiology/tiva3.html


In a three compartment model, several distinct phases can be distinguished. The first phase is
characterised by very rapid movement of the drug from the plasma to certain tissues which are well perfused (vessel-rich group). This rapid "distribution" phase occurs within one or two circulations of the drug in the body and defines the peak drug concentrations. The second phase or slow distribution phase is caused by the equilibration of the blood with tissues which are less well perfused. During this phase there is not an equilibrium. Drug is being distributed from the plasma into more slowly equilibrating tissues and redistributed to the plasma from the most rapidly equilibrating tissues. If a drug has very limited ability to penetrate membranes, distribution factors can become rate limiting in the equilibrium of the blood concentration with the tissues.
http://www.euroanesthesia.org/education/rc_amsterdam/09rc3.H...


The pharmacokinetics of propofol have been evaluated extensively in a variety of disease states and patient groups after either bolus doses or continuous infusions (Bryson et al. 1995, Schüttler 1990, Simons et al. 1988, Gepts et al. 1987). Propofol undergoes rapid and extensive distribution and a rapid metabolic clearance.

After a bolus dose, there is a rapid, initial distribution phase which represents distribution to highly perfused organs such as the brain (effect site). This is followed by a slower, second phase representing redistribution to less well perfused tissues such as muscle. Significant metabolism occurs during this second phase. Recovery from anaesthesia is due to extensive redistribution from the brain and to metabolic clearance.

Figure 3 Pharmacokinetics: open, three-compartment model: schematic representation.