What is the Role of DMPK Research for Successful Drug Discovery and Development?

What is the Role of DMPK Research for Successful Drug Discovery and Development?

Drug metabolism and pharmacokinetic (DMPK) properties of the drug are analyzed to know half-life, bioavailability, metabolic, and clearance profile of a drug that is being tested for the market. The essential goal of DMPK studies is to evaluate various compounds of drug substance, know its intrinsic properties, and then achieve metabolism studies. If this DMPK research is suboptimal or not effective, it leads to the discontinuation of many leading drugs. This also means that lower quality drugs may cause unsolicited side-effects and toxicity.

In this article, we will discuss the role of ​DMPK pharmacokinetics in successful drug discovery.

Understanding DMPK and ADMET DMPK is a discipline which was earlier associated with the evaluation of the safety of drug development. But, it has now become a core function for drug discovery and development. About 20-25 years ago, if DMPK properties were not of the highest quality, it was seen as a contributor to the potential failure of new trails. This led to the realignment of DMPK to assist discovery of drugs by choosing the right drug candidates for clinical trials.

This simply means that in vivo PK outlining and in vitro ADMET together contribute to finding new molecular entities. The whole process leads us to suitable drug metabolism, which assists in selecting the necessary drug candidate.

Another factor that contributes to the progress of DMPK research is ADMET (absorption, distribution, metabolism, excretion, and toxicity). These properties help in avoiding drug-drug interactions and increasing drug design. ● The amount of drug absorbed, which is also known as bioavailability. ● The site of distribution of drug along with the rate of distribution. ● The time of metabolization of the drug along with the mechanism used, which may or may not be toxic. ● The process of drug excretion from the body. ● The toxic impact of the drug on the body and its organs.

Role of DMPK In Drug Discovery and Development From the past few years, pharmaceutical companies have been increasingly utilizing DMPK parameters in the early stages of drug discovery and research pipeline. This is due to the fact that development laboratories are concentrating on molecules that have

high affinity, high bioavailability, low clearance, and optimal metabolic properties.

Owing to the effectiveness of DMPK in early stages, the efficiency of in vitro metabolism and pharmacokinetics studies increase. Take LC/MS/MS (Liquid Chromatography-Tandem Mass Spectrometry) for example. This process gives sensitivity analysis for multiple compounds and their samples.

Hence, adding to the total drug candidates that will progress through the discovery and development phases of the drug.

Overall, with the satisfactory safety profile, the potency of the target protein, minimum drug-drug interaction, and balanced PK parameters, the chances of a drug becoming successful increases.

Looking at the complexity and challenges of the industry, the drug attrition rates are considerably high. So, bringing safe-to-use medicines to the market via sustainable means and effective therapies is a necessity. The poor efficacy and development of reactive metabolites along with suboptimal DMPK leads to severe side-effects. Hence, it is necessary to optimize DMPK factors in early stages of drug development for rational drug design and development.