Pharmacodynamic objectives

Pharmacodynamic objectives Pharmaceutical objectives Pharmacokinetic objectives... 

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. ... 

Proponents of the clinical mirror theory of bioequivalence would like to see increased emphasis placed on quantification of pharmacodynamic values. In some instance we can readily identify how reliable and relevant pharmacodynamic values can be measured. For example, for an antihypertensive drug, measurement of blood pressure changes can be conveniently, inexpensively and objectively determined. However, for other types of drug (e.g., antidepressants) it is not easy to conceive any simple pharmacodynamic attributes that could be readily determined. 

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. 

Any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of an investigational product, and/or to identify any adverse reactions to an investigational prodnct, and/or to study absorption, distribution, metabolism, and excretion of an investigational product with the object of ascertaining its safety and/or efficacy. 

The analysis of samples obtained from physiological matrices has been the object of many reports on the use of Rlk]. This use can be expected to expand in response to the need to understand the pharmacodynamics and pharmacokinetics of various pharmaceutical agents. In addition, the versatility of RPC will facilitate the analysis of various metabolites and,... 

The indirect pharmacodynamic interactions are unrelated to the effects of the object drug, for example ... 

The goal of therapeutics is to achieve a desired beneficial effect with minimal adverse effects. When a medicine has been selected for a patient, the clinician must determine the dose that most closely achieves this goal. A rational approach to this objective combines the principles of pharmacokinetics with pharmacodynamics to clarify the dose-effect relationship (Figure 3-... 

The primary objective of the early efLcacy studies is to validate the pharmacology model with a compound that is known to interact with the desired receptor and develop the Pharmacokinetics-Pharmacodynamics (PK-PD) relationship for further screening during lead optimization (Neervan-nan, 2006). It is essential that the excipients selected forthe vehicle do not interfere with the measured end points especially, for a disease-relevant animal model that has no clinically effective drugs to validate an animal model. In this situation, vehicles should be used as negative controls in the studies. 

The next stage of assessment is multidose tolerance (MDT) study. The objective of this study is to assess pharmacodynamic and pharmacokinetic effects and to collect data for any adverse event observed. For this assessment, a range of doses is administered with placebocontrol to healthy volunteers for 7-14 days. The intention of these studies is to assess any potential saturation of metabolism. 

Before discussing the specific pharmacokinetics and pharmacodynamics of each class of antineoplastic agents, several fundamental concepts and therapeutic objectives will be considered first. 

---