Medicine Digests
The idea that drug concentrations could be measured and used to guide therapeutic decisions was first applied to quinidine when it was used to convert the cardiac rhythm of patients with atrial fibrillation to sinus rhythm (Sokolow & Ball 1956).
Although quinidine is rarely used for this purpose today, because of the advent of DC cardioversion, this study is still almost unique because it defined a target concentration based upon both the probability of therapeutic success and of toxicity.
A concentration of 8 rag/ L was shown to have an 80% chance of converting atrial fibrillation to sinus rhythm and a 20% chance of some serious toxicity. No attention was paid to pharmacokinetics, The target concentration was chosen on the basis of pharmacodynamics, i.e. the effects, both good and bad, observed at particular concentrations.
Rational therapeutics – the aim of rational therapeutics is to achieve the desired effect with the correct dose. The foundation of decision making is based on pharmacokinetics and pharmacodynamics which provide the rational principles to link dose and effect through drug concentration.
Rational therapeutics can be defined as the administration of the correct dose to achieve the desired effect. The target concentration concept is at the centre of rational therapeutics where it links dose to effect. Pharmacokinetics is the science that links dose and concentration by defining the processes of drug distribution (volume of distribution) and elimination (clearance).
Pharmacodynamics, on the other hand, is the science linking concentration to effect by defining the maximum effect of the drug (Emax) and the sensitivity of the target organ (as determined by the EC50; M£ the concentration producing 50% of Emax).
Therapeutic drug monitoring can now be placed at the centre of this therapeutic triangle. This incorporates information about doses, concentrations, and effects in an individual and integrates these data to estimate more precisely the pharmacokinetic (volume of distribution, clearance) and pharmacodynamic (Emax, EC50) parameters in that individual. These new values can then be used to predict the consequences of future dosing decisions and thus enable the selection of a suitable dose to achieve the desired effect, i.e. rational therapeutics.
Data, Distribution, Dose, Drug, Effect, Foundation, Monitoring, Rational, Science, Selection, Sensitivity, Studies, Therapeutic, Toxicity, Value
