Pharmacodynamics, definition

The overall objective of clinical trials is to establish a drug therapy that is safe and effective in humans, to the extent that the risk-benefit relationship is acceptable. The ICH process has developed an internationally accepted definition of a clinical trial as Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy. ... 

Phase I studies evaluate the pharmacokinetics and safety of the drug in a small number (tens) of healthy volunteers. Phase I studies are sometimes conducted in a small patient population (Proof of Concept studies) with a specific objective such as the validation of the relevance of preclinical models in man. The purpose of these studies may be the rapid elimination of potential failures from the pipeline, definition of biological markers for efficacy or toxicity, or demonstration of early evidence of efficacy. These studies have a potential go/no-go decision criteria such as safety, tolerability, bioavailability/PK, pharmacodynamics, and efficacy. Dosage forms used in Phase I or Proof of Concept studies must be developed with the objectives of the clinical study in mind. 

There is a diversity of opinion regarding definitions and benefits of pharmacogenetics and pharmacogenomics.1 3 For example, pharmacogenetics is often considered to be the study of inter-individual variations in DNA sequence related to drug absorption and disposition (pharmacokinetics, PK) or drug action (pharmacodynamics, PD). Polymorphic variation in the genes that encode the functions of transporters,... 

Phase III studies represent the confirmatory phase of drug development, which takes several years and usually involves several thousand patients at multiple trial centers. Large patient numbers are required in these trials to provide convincing documentation of clinical efficacy and safety, a more complete adverse event profile and covariates and estimates of variability in dose response relationship due to individual differences in pharmacokinetics and pharmacodynamics. They are aimed at definitively determining a drug s effectiveness and side-effect profile. Most of these studies are double-blind and placebo-controlled, sometimes with the option of open-label long-term extensions. 

Adverse drug reactions and drug interactions W McCaughey Introduction Definitions Adverse reactions Drug interactions Pharmacokinetic Pharmacodynamic Clinically important interactions INTRODUCTION... 

For definitions see Section 2.7. The factors affecting the pharmacokinetic phase are ADME. The factor affecting the pharmacodynamic phase is the stereoelectronic structure of the drug molecule. 

Clinical trials and clinical trial authorizations in the European Union are controlled under the Clinical Trial Directive, 2001/20/EC [9], and all member states are bound by its requirements. Under the provisions of the Directive, a clinical trial is an investigation in human subjects that is intended to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effects of one or more medicinal products, identify any adverse reactions or study the absorption, distribution, metabolism, and excretion, with the object of ascertaining the safety and/or efficacy of those products. This definition includes pharmacokinetic studies. 

The broad definition of a drug as "any chemical that affects living processes" (Benet, Mitchell, and Sherner 1990a) is helpful in understanding the relationship between the body and administered medications. This is a fluid and interactive process, composed of two elements pharmacodynamics and pharmacokinetics. 

Reversible interaction with the biological object results in pharmacodynamic effects which, in certain circumstances, may be undesired and therefore must be classed as toxic. Chemical lesions, with very few exceptions, are classed as definitely toxic. 

The chemical properties and hence the chemical structure of a compound definitely determine its participation in the partial processes making up the various phases of action. The relationship of structure to action is therefore a fundamental characteristic of the action of pharmaca. The apparent absence of such a relationship can only be due to deficient methods of investigation and to the multiplicity and complexity of the processes involved. The structure-action relationship will be found to emerge more clearly if it is studied with regard to particular part-processes such as those involved in pharmacon metabolism, in pharmacon distribution, and in pharmacodynamics. Such a study involves the use of simple, isolated test systems. 

As mentioned in two critical reviews on transcultural psychopharmacology of the TCAs (Pi et al. 1993a Sramek and Pi 1999), the concept of differences between Asian and non-Asian populations in the pharmacokinetics and pharmacodynamics of TCAs has gained support from clinical reports and controlled studies. Whether these differences are due to ethnicity, pharmacokinetics, pharmacodynamics, environmental factors, or shortcomings of study design (such as small sample size) is not definitely known. Although recent studies of CYP polymorphism support the possibility of genetic differences, future studies will need to address these issues. 

Response Surface Model A dose-response surface is an extension of dose-response lines (isobols) to three dimensions. In this representation there can be a dose-response surface representing additivity and surfaces above and below suggesting deviation from additivity. Tam et al. [90] studied the combined pharmacodynamic interactions of two antimicrobial agents, meropenem and tobramycin. Total bacterial density data, expressed as CFU (colony forming units), were modeled using a three-dimensional surface. Effect summation was used as the definition of additivity (null interaction hypothesis) and the pharmacodynamic model was assumedi to take the functional form... 

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