Time Course of Drug Response

Therapeutic drug responses are a consequence of drug exposure. Exposure describes the intensity and time course of drug treatment. Most clinicians and patients behave as if they believe drug exposure is defined by the drug dose. However, a central dogma of clinical pharmacology is that drug actions are determined by drug concentration. Events leading up to such concentrations include the therapeutic consultation between patient and prescriber, the patient's decision to obtain and take the medication, and the time course of delivery and loss of drug from the site of action. The act of taking a drug dose is only one step in this chain of events and provides only part of the information needed to predict the time course of response. Pharmacokinetics provides a rational framework for understanding how the time course of observable drug concentration (usually in plasma) is related to the dose. The principles of pharmacodynamics described in Chapter 20 provide a companion framework for understanding the relationship between concentration and response. However, pharmacokinetics and pharmacodynamics are not enough by themselves to describe the time course of drug response for two main reasons. (1) Plasma is not the site of action of most drugs, so responses will be delayed in relation to pharmacokinetic predictions of plasma concentrations. The only exceptions are a limited number of drugs (e.g., heparin) whose action directly affects physical components of plasma. (2) The action of a drug is not the same as the drug response. In many cases, a network of events links receptor activation to physiological changes. These in turn are linked via complex pathophysiological mechanisms, often including homeostatic feedback, before the appearance of either therapeutic or adverse pharmacologic responses.