Measurement of drug effects

Is there a relationship between plasma concentrations and a relevant measure of drug effect ... 

An in vitro or ex vivo measure of drug effect, for example, mean inhibitory concentration (MIC) of an antimicrobial against bacterial culture inhibition of ADP-induced platelet aggregation with a fibrinogen receptor antagonist. 

The non-linear mixed effects model is the most widely used method and has proven to be very useful for continuous measures of drug effect, categorical response data, and survival-type data. The nonlinear mixed-effects modeling software (NONMEM) introduced by Sheiner and Beal is one of the most commonly used programs for population analysis. A detailed review of software for performing population PK/PD analysis is available. ... 

Moskowitz, H, (1984). Attention tasks as skills performance measures of drug effects. Br. J. Clin. Pharmacol, 18(Suppl 1), 51S-61S. 

Potency, the concentration (usually molar) of a drug that produces a defined effect. Often, potencies of agonists are defined in terms of EC50 or pECso values. The potency usually does not involve measures of maximal effect but rather only in locations along the concentration axis of dose-response curves. 

Tzschentke, T.M. Measuring reward with the conditioned place preference paradigm a comprehensive review of drug effects, recent progress and new issues. Prog. Neurobiol. 56 613, 1998. 

The particular models used in drug targeting research are dealt with in Section 13.3, and quantitative measures of the effectiveness of drug targeting are described in Section 13.4, followed by a discussion relating to their application in Section 13.5. 

PK models (Section 13.2.4), PD models (Section 13.2.5), and PK/PD models (Section 13.2.6) can be used in two different ways, that is, in simulations (Section 13.2.7) and in data analysis (Section 13.2.8). Simulations can be performed if the model structure and its underlying parameter values are known. In fact, for any arbitrary dose or dosing schedule the drug concentration profile in each part of the model can be calculated. The quantitative measures of the effectiveness of drug targeting (Section 13.4) can also be evaluated. If actual measurements have been performed in in-vivo experiments in laboratory animals or man, the relevant model structure and its parameter values can be assessed by analysis of plasma disappearance curves, excretion rate profiles, tissue concentration data, and so forth (Section 13.2.8). 

If an appropriate model is selected and the model parameters are known, the time course of the drug concentration in each compartment (PK models) and the drug effect (PK/PD models) can be calculated for any dosing regimen. In addition, the relevant measures of the effectiveness of drug targeting can be calculated (see Section 13.4). 

For practical purposes, measures of the effectiveness of drug targeting are required. Such measures have been derived based on the pharmacokinetic profiles of the drug targeting system and that of the active drug. 

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