ADME trials

In summarizing the ADME trials, tabulate species, strain, and dose comparison data by the following ... 

Absorption, distribution, metabolism, and excretion (ADME) trials... 

An important part of the optimization process of potential leads to candidates suitable for clinical trials is the detailed study of the absorption, distribution, metabolism and excretion (ADME) characteristics of the most promising compounds. Experience has learned that physico-chemical properties play a key role in drug metabolism and pharmacokinetics (DMPK) [1-3]. As an example, physicochemical properties relevant to oral absorption are described in Fig. 1.1. It is important to note that these properties are not independent, but closely related to each other. 

The drug discovery and development processes are time consuming and costly endeavors. It has been reported that on average it takes 10 to 15 years and costs more than 800 million to bring a molecule from discovery to market.12 Compounds fail for various reasons. One that accounts for a reported 40% of failures in clinical trials is poor pharmacokinetics.3 In an effort to improve the number of compounds that exhibit optimal absorption, distribution, metabolism, elimination (ADME), and pharmacokinetic (PK) properties and reach development, drug metabolism and pharmacokinetic scientists continually implement new technologies and compound screening approaches. 

Because DMPK properties vary among different species, in vitro human and animal data and in vivo animal data cannot always be extrapolated to human in vivo responses. The three main reasons that drugs fail during clinical trials are (1) lack of efficacy, (2) unacceptable adverse effects, and (3) unfavorable ADME properties. Hence, clinical development is necessary to establish solid experiment-based human exposure and safety data through both short- and long-term monitoring. 

Small-scale clinical trials with healthy volunteers to determine safety, tolerability, and ADME. 

For kinetics, an information on exposure data (AUC) in animals prior human clinical trials is needed while ADME data are needed at completion of Phase I (Human Pharmacology) studies. 

Absorption, Distribution, Metabolism and Excretion (ADME) In clinical trials, the bodily processes studied to determine the extent and duration of systemic exposure to a drug. 

A list of literature references on toxicity, pharmacological action, ADME and cliniced trials for the active ingredients concerned, as well as an outline of the list content and the results of evaluation shall be required. 

---