Practical Pharmacokinetics of Anesthetic Drugs
Physiologic Concepts
Figure 43-1 Schematic representation of pharmacokinetic processes responsible for changing plasma drug concentrations.
Pharmacokinetic Parameters and Dosage Regimens
A parameter may be defined as a quantifiable characteristic of a system that is used as input for a predictive model. In pharmacokinetic modeling, parameters are quantitative estimates of the rate and extent of distribution, elimination, and absorption, which are used to predict plasma drug concentrations for specific drug dosages in individuals or groups of animals. These pharmacokinetic parameters are estimated by fitting a pharmacokinetic model to observed data and are then used to construct dosage regimens that will achieve a specified target plasma concentration. Examples of target concentrations include the minimum inhibitory concentration (MIC) (or a multiple thereof) for antimicrobial drugs or, in the case of drugs used to induce anesthesia, concentrations associated with the desired depth and duration of anesthesia.
Single Intravenous Dose
A graphic representation of the time–concentration data for a hypothetical drug following IV administration is shown in Figure 43-3. Note that the relationship between the x (time) and y (concentration) variables becomes linear if the y-axis is transformed to a logarithmic scale. Also, note that the concentration declines over time at a constant rate (see Figure 43-3). The data may, therefore, be described using a simple monoexponential mathematic equation that is conventionally referred to as a one-compartment pharmacokinetic model (see Equation 1). Drugs that can be described using a one-compartment model typically equilibrate rapidly between blood and tissues. This makes it possible to describe their disposition as the drug being injected into a single compartment of uniform liquid with the dose distributing instantaneously and homogeneously throughout this compartment and the drug being eliminated from the compartment immediately after injection.
Figure 43-3 Typical time–concentration profile of a drug best described by using a one-compartment model on a linear (A) and a semilogarithmic (B) scale.