Drug dose-response relationships parameters

Another difference from drug therapy is that the dosing interval of a nutritional supplement is often not a critical parameter for a positive outcome. This lack of a strong dose-response relationship is an important consideration in setting of standards for dietary supplements and is in stark contrast to the situation for drug products. 

There are severai pharmacokinetic parameters that are reievant to the ciinicai use of drugs. These heip quantify a dose-response relationship, or... 

Dose-escalation studies performed in an early phase of drug development provide preliminary information to explore pharmacodynamic parameters at different dose levels up to the MTD. If the focus of a study is on the relationship between the pharmacokinetic and pharmacodynamic parameters (rather than on dose response relationships), then the term PK PD studies is used. 

Fig. 1.5 Illustration of the simulation and analysis of a virtual trial outcome. The solid line represent the true dose-response relationship based on a sampled set of parameters from the joint posterior distribution of the model parameters. The circles represent the simulated drug effects in the patients included in the trial on the basis of the true" model parameters and the errors bars...

Pharmacokinetics (PK) can be a major source of variability in the dose response relationship. It manifests itself in interindividual differences in the plasma concentration-time profile of a drug. Factors which lead to variability in the ADME parameters are therefore of importance in understanding overall variability in PK. 

The parameters are eo (baseline response), Emax (maximum response), and ed50 (the dose that achieves 50% of maximum drug effect). Npuff is the number of puffs. In addition, it is assumed that the active ingredient in the test drug will be proportional to that of the reference drug, with a multiplication factor F. Under this assumption, the dose-response relationship for both the test and the reference drug can be written jointly as follows ... 

An understanding of metabolism and kinetics is pertinent to the overall goal of this Symposium, inasmuch as the rate and pathway of the biotransformations in a given species are important determinants of the dose-response relationship of the therapeutic agent and its elimination kinetics and terminal residues. Clearly, the current literature reveals that biotransformation reactions play a role in the overall behavior of chemicals and drugs in aquatic species and that the manipulation of the rates of these reactions by inducers or inhibitors of biotransformation can significantly affect important kinetic and therapeutic parameters, such as steady-state tissue levels, persistence, and metabolite profiles. 

The population approach is a new point of view in clinical drug evaluation and therapy. It emphasizes the estimation of parameters describing the dose-concentration-response relationship both between and within patients (including average behavior and variability). The population approach recognizes vari-... 

Interpretation of findings from these studies will be aided by a good understanding of dose/concen-tration and concentration/response relationships for both desirable and undesirable drug effects. In certain instances, reliance on endpoints other than pharmacokinetic measures/parameters may be useful... 

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