The main goal of drug development is to obtain a compound with a therapeutic effect that we can administer to patients. A drug must reach the site of action, exert its pharmacological effects and be eliminated within a reasonable time. Characterization of ADME/DMPK properties helps to explore and explain how pharmacokinetic processes occur, in order to provide new drug safety considerations on which risk-based assessments can be made.
Non-clinical in vivo DMPK (ADME & QWBA).
The role of pharmacokinetics (PK) in discovery is to support the optimization of ADME/DMPK properties of lead compounds with the ultimate goal of obtaining a clinical candidate that achieves an adequate concentration-time profile for the efficacy profile and the desired safety.
NCA analysis for PK and TK data.
The level of confidence in predictions increases with the level of understanding of PK/TK and PK/TK/PD of New Chemical Entities (NCEs) in relation to pathophysiology and the ability to propose safe and efficacious doses and dosing schedules in responsive patient populations.
PK/PD studies (exposure- response).
Extensive characterization of lead compounds to identify key PK parameters also includes early generation of PK/PD relationships linking in vitro potency and target exposure/engagement with expression of pharmacological activity (mode of action) and efficacy in in-vivo studies.
Once the robust PK/PD relationship in in vivo PD models has been constructed, it is translated to anticipate pharmacologically active therapeutic dose (exposure/ concentrations) in patients and dosing regimen which is also based on the prediction of PK behavior in humans.
ADME models.
In combination with an evaluation of physico-chemical/in-silico properties, ADME models (caco-2, DDI…) allow a better mechanistic understanding of the PK characteristics of a compound or a class of compounds. Indeed, an earlier level of use of data from in vitro and ADME models allows for better description and estimation of the drug concentration profile to support and aid in the go-no-go decision.
Drug design-Candidate selection.
PK/PD profiles of drugs are influenced by physicochemical properties, formulation, route of administration, patient intrinsic and extrinsic factors (eg, organ dysfunction, diseases, concomitant medications, food)
PK/PD/TK
Strategic & expertise input
The right compound in the right dosage at the right time:
To achieve maximum return on investment, it is critical that DMPK concepts are both appropriately integrated into the compound design process and that compound selection is focused on accurately predicting likely patient outcomes.
- Provide sufficient preclinical evidence on the quality, safety and efficacy of the drug compound to be tested in humans
- Demonstrate that it can be used safely in humans (healthy volunteers and patients) and that its pharmacokinetic profile justifies further development and provide evidence that drug shows sufficiently convincing positive signs of a relevant therapeutic effect in the target patient population to enable its development at the end of development