DMPK stands for Drug Metabolism and Pharmacokinetics. A DMPK profile of prospective new drugs is essential to know its bioavailability, its half-life, and clearance and metabolic profile. An improper DMPK profile causes discontinuation of drug leads and unwanted side effects.
The Goal of DMPK Studies
Drug Metabolism and Pharmacokinetics studies deal with absorption, distribution, metabolism, and excretion (ADME) of the new drug lead. Its purpose is the screening of multiple compounds, evaluating their DMPK properties, and performing additional metabolic studies on a set of screened out compounds that have the potential to proceed for drug development.
Tips for DMPK Studies
Recent drug discovery program advocates DMPK assay in the early stages of the process. R & D labs are striving to design molecules with a high target affinity, low rate of clearance, and high oral bioavailability for which, DMPK studies are essential in the earlier stages of drug discovery program. DMPK studies generally involve evaluation of the below-mentioned parameters about the prospective new drug lead:
It is a valuable physicochemical property of a potential new drug that plays a role in absorption, CNS penetration, distribution, membrane penetration, plasma protein binding, partitioning into other tissues or organs such as the liver and solubility.
Aqueous solubility reflects the bioavailability of the compound. The ability of a drug molecule to dissolve in a cellular solvent is essential to achieve the desired concentration of drug in body circulation.
Hepatic Microsome Stability
This assay makes use of Microsome, a sub-cellular component of the liver, to assess the metabolic fate of drug compounds. This assay indicates how long a molecule will remain circulating in plasma in a host body.
Plasma enzymes, particularly hydrolyzing and an esterase, are also capable of degradation of the new drug molecule. Hence, the stability of the drug molecule in plasma is an important parameter.
Plasma Protein Binding
The efficacy of a drug, its metabolism, and its pharmacokinetic properties are affected by the binding of test compounds to plasma proteins. In most of the cases, the drug efficacy is proportional to the concentration of the free drug (unbound), rather than the level of total medicine in plasma. The effectiveness of that compound may be significantly less if the drug is highly bound to plasma proteins. Less amount of medication is available to reach the target.
Screening Cytotoxicity / Hepatotoxicity Test
The in vitro Cytotoxicity test takes the help of primary hepatocytes. It is an excellent method to identify the cytotoxic potential of a test substance. The ATP-lite 1step Cytotoxicity Assay measures the number of live cells in culture wells.
Evaluating the permeability of the new drug through a cell monolayer indicates its intestinal permeability and oral bioavailability. PAMPA, which stands for The Parallel Artificial Membrane Permeability Assay, is a good test for this.
It is a good Laboratory practice to carry out DMPK studies in the early stages of designing and development of new drugs of potential.