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Definitive Role of DMPK Studies For Successful Drug Discovery And Development

DMPK or Drug Metabolism and Pharmacokinetics is a scientific discipline associated with the evaluation of safety parameter throughout the process of drug development. In the last few decades, the DMPK studies have contributed a lot towards the success of the drug discovery and development process. There are three prime ways through which the DMPK studies helps a researcher with the drug discovery process

  • Firstly, such studies are routinely employed in the early drug discovery and synthesis steps.
  • Secondly, these studies provide information about metabolic enzymes of the drug, transporters, and differences between individual and species.
  • Thirdly, optimization of DMPK properties are developed, improved, and applied throughout different drug development stages.

Under DMPK studies, ‘drug-like’ properties usually applies to absorption, adequate distribution, metabolism, and complete elimination from our system.

There are different ways through which the DMPK process can be easily incorporated into drug discovery. Firstly, certain pharmaceutical compounds are selected and based on their potency. Selectivity characteristics and DMPK data are obtained from it. In another approach, the DMPK assay is performed on all the synthesized compounds.

What is in silico DMPK?

According to the FDA, a good drug is defined as the one which is both safe and effective. The safety and efficacy of the pharmaceutical product are determined by an optimal balance achieved between its potency, degree of selectivity, and the effects of drug exposure at the site of the molecular target. Drug exposure towards the molecular target is determined by its absorption, metabolism, and ability to cross the blood-brain barrier.

In vitro DMPK –

To accomplish HTS screening, different molecules are required, which are usually generated through a wide array of modern synthesis methods. The in vitro potency of any pharmaceutical product can be enhanced by introducing a lipophilic moiety to fit rightly into a receptor molecule.

In vivo DMPK –

These DMPK assays function as screening techniques for eliminating the administration of both unsafe and ineffective compound to humans. These usually have low throughputs; however, advancements made in the analytical instrumentation have resulted in improving their overall performance.  

Clinical DMPK –

Clinical DMPK data are used for the evaluation of both pre-clinical and clinical parameters, contributes towards the process of drug monitoring, aids in exposure assessment, and bridging the gap between exposure to toxicity and safety profiling.

To sum up, the role of DMPK assays across the four significant drug discovery and development phases are tabulated below –

PhaseStudy
Phase 1The starting dose
Maximum dose
Linear kinetics
Dose-range studies
Definitive kinetics
Phase 2Drug-food and drug-drug interactions
PK/PD relationships
Sex differences
Dose-response curve
Genetic polymorphism
Absolute bioavailability
PK/PD profiling of population
Phase 3Sub-group analysis
Final population study using PK/PD model
Individual sources of variability and risk factors
Special populationsEffects of disease
Final dose form PK
Phase 4Line extensions
Pharmacovigilance
Dose form improvements
Post-marketing studies
Modified release preparations
Prescriptions of OTC
Change of formulationDrug interactions

Thus, the evolutions introduced in DMPK studies have led to greater contributions to everything right from selection of the lead drug to its optimization as it did in the past.

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