Guide to Good Prescribing - A Practical Manual
(1994; 115 pages) [French] [Spanish] View the PDF document
Table of Contents
View the documentAcknowledgments
View the documentWhy you need this book
Open this folder and view contentsPart 1: Overview
Open this folder and view contentsPart 2: Selecting your P(ersonal) drugs
Open this folder and view contentsPart 3: Treating your patients
Open this folder and view contentsPart 4: Keeping up-to-date
Close this folderAnnexes
Close this folderAnnex 1: Essentials of pharmacology in daily practice
View the documentIntroduction
Open this folder and view contentsPharmacodynamics
Close this folderPharmacokinetics
View the documentThe Cp/time curve with a therapeutic window
Open this folder and view contentsDrug treatment
Open this folder and view contentsSpecial features of the curve
View the documentAnnex 2: Essential references
Open this folder and view contentsAnnex 3: How to explain the use of some dosage forms
Open this folder and view contentsAnnex 4. The use of injections
View the documentBack Cover
 
The Cp/time curve with a therapeutic window

Two horizontal lines can be placed over the Cp/time curve, indicating therapeutic threshold and ceiling. The space between these two lines is called the therapeutic window (Figure 13). Drug treatment aims at plasma concentrations within this therapeutic window. The possible variables to be considered are therefore (1) the position and the width of the window, and (2) the profile of the curve.


Figure 13: Cp/time curve and therapeutic window

Therapeutic window

The position and the width of the window are determined by pharmacodynamic factors (Figure 14). The position of the window may shift upwards in case of resistance by the patient or competitive antagonism by another drug: a higher plasma concentration is needed to exert the same effect. The window can shift downwards in case of hypersensitization or synergism by another drug: a lower plasma concentration is needed.


Figure 14: Place and width of therapeutic window

The width of the window may also vary. It may become narrower in case of a decreased safety-margin. For example, the therapeutic window of theophylline is narrower in small children than in adults. A broader window usually has no consequences.

Curve

The profile of the curve is determined by four factors: Absorption, Distribution, Metabolism and Excretion. These are usually referred to as ADME factors. Although most treatments consist of more than one dose of a drug, some pharmacokinetic parameters can best be explained by looking at the effect of one dose only.

One of the most important parameters is the half-life of a drug (Figure 15). Most drugs are eliminated by means of a first-order process. This means that per unit of time the same percentage of drug is eliminated, for example 6% per hour. The half-life of a drug is the time it takes to decrease the plasma concentration to half of its initial value. With 6% per hour the half-life is about 11 hours (if no more of the drug is given in the meantime). After 2 half-lives (22 hours) it will be 25%; after 3 half-lives 12.5%; and after 4 half-lives 6.25%. If the original plasma concentration falls within the therapeutic window, a decline to 6.25% will usually be far below the therapeutic threshold. For this reason it is usually said that drugs no longer have a pharmacological effect 4 half-lives after the last dose.


Figure 15: Half-life of a drug

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