Time course of drug 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 18 provide a companion framework for understanding the relationship between concentration and response. However, these scientific disciplines are not enough to describe the time course of drug response, for two main reasons ... 

So far we have focused our attention on the time course of drug effect. While the study of these effects can be helpful in understanding the mechanism of drug action and factors affecting efficacy and potency, it usually does not provide information on how drug exposure influences therapeutic response. 

Levy (1964), Jusko (1971) and Smolen (1971, 1976) described the analysis of dose-response time data. They developed a theoretical basis for the performance of this analysis from the data obtained from the observation of the time course of pharmacological response, after a single dose of drug, by any route of administration. Smolen (1976) extended the analysis to application of dose-response time data for bioequivalence testing. 

However, there are other major factors in determining the dosing regimen, such as the nature of the concentration-response relationship for both efficacy and toxicity (therapeutic window) and commercial/ compliance factors. There are additional reasons why caution should be applied in assuming an efficacy-time profile from a given plasma concentration-time profile. Some reasons why the time course of drug concentration and effect may differ are given in Table 5.1. 

Figure 6 Time course of drug effect after a single intravenous dose of a drug that obeys the one-compartment open pharmacokinetic model, and the response is described by the simple Emax model.

PuRVES, R. D., 1977, The time course of cellular responses to iontophoretically applied drugs, /. Theor. Biol. 65 327-344. 

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