Principles of Dose Selection The desired goal of therapy with any drug is to maximize the likelihood of a beneficial effect while minimizing the risk of adverse effects. Previous experience with the drug, in controlled clinical trials or in postmarketing use, defines the relationships between dose (or plasma concentration) and these dual effects and provides a starting point for initiation of drug therapy. Figure 5-1 illustrates the relationships among dose, plasma concentrations, efficacy, and adverse effects and carries with it several important implications: 1. The target drug effect should be defined when drug treatment is started. With some drugs, the desired. | Chapter 005. Principles of Clinical Pharmacology Part 6 Principles of Dose Selection The desired goal of therapy with any drug is to maximize the likelihood of a beneficial effect while minimizing the risk of adverse effects. Previous experience with the drug in controlled clinical trials or in postmarketing use defines the relationships between dose or plasma concentration and these dual effects and provides a starting point for initiation of drug therapy. Figure 5-1 illustrates the relationships among dose plasma concentrations efficacy and adverse effects and carries with it several important implications 1. The target drug effect should be defined when drug treatment is started. With some drugs the desired effect may be difficult to measure objectively or the onset of efficacy can be delayed for weeks or months drugs used in the treatment of cancer and psychiatric disease are examples. Sometimes a drug is used to treat a symptom such as pain or palpitations and here it is the patient who will report whether the selected dose is effective. In yet other settings such as anticoagulation or hypertension the desired response is more readily measurable. 2. The nature of anticipated toxicity often dictates the starting dose. If side effects are minor it may be acceptable to start at a dose highly likely to achieve efficacy and downtitrate if side effects occur. However this approach is rarely if ever justified if the anticipated toxicity is serious or life-threatening in this circumstance it is more appropriate to initiate therapy with the lowest dose that may produce a desired effect. 3. The above considerations do not apply if these relationships between dose and effects cannot be defined. This is especially relevant to some adverse drug effects discussed in further detail below whose development is not readily related to drug dose. 4. If a drug dose does not achieve its desired effect a dosage increase is justified only if toxicity is absent and the likelihood of .
