Impact of Psychoactive Drugs

Despite the enormity of the pharmaceutical industry and the vast array of psychoactive substances used in an illicit manner, the mode of action of drugs in the body can be understood by reference to basic pharmacokinetic

Pharmacokinetics. Fig. 1. Calculation of area under the curve (AUC) using the Trapezoidal Rule showing a linear plot of concentration of drug in plasma (Cp) versus Time showing AUC and AUC segment ( c0208.html).

The AUC is very useful for calculating the total body clearance (► CL) and the ► apparent volume of distribution (see later). In the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the more frequent the sampling, the closer the trapezoids to the actual shape of the concentration-time curve (Fig. 1). Intravenous administration of a developmental drug can provide valuable information on fundamental pharmacokinetic parameters, but may often be biased towards an apparent rapid peak plasma concentration and short lasting exposure when compared to oral administration.

Compartmental Analysis

Compartmental pharmacokinetic analysis use kinetic models to describe and predict the concentration-time curve. The advantage of compartmental to some non-compartmental analysis is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. Compartment-free modeling based on curve stripping does not suffer this limitation. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and ► first-order elimination kinetics, (Neligan 2009) where a constant fraction of the drug in the body is eliminated per unit time as shown in Fig. 2.

Pharmacokinetics is predominantly studied in a laboratory setting using advanced chromatographic

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