Pharmacological profiling PK/PD
Preclinical pharmacology studies are performed in order to pinpoint the therapeutic value of a new drug entity on a specific disease.
In a first step, Polyphor’s pharmacological profiling focuses on in vitro assays:
In vitro pharmacological assays cover a broad range of targets including receptors, ion channels, transporters, enzymes and intracellular signaling pathways.
These assays are used to identify lead compounds, to characterize the level of ortholog potency, to define mechanism of action, and also to identify potential off-target activities giving an initial indication safety.
In a second step, Polyphor’s pharmacological profiling focuses on in vivo assays:
In vivo pharmacological studies are the basis and main objective of preclinical pharmacology. These studies are performed in order to investigate the efficacy of a new drug entity in pathological conditions on a specific disease.
Efficacy studies are performed in several relevant and validated animal disease models that mimic the pathological signs and symptoms in humans for a given disease. The compound under investigation is administered by different routes at several doses and a dose-response correlation is sought.
Before entering into such preclinical pharmacology studies Polyphor assesses the pharmakokinetics (PK) of a compound administered to an animal to address important questions, such as:
- How is a compound distributed in the body?
- How quickly is a compound removed (cleared) from the body?
- What is the impact of the route of administration?
- What is the bioavailability of a compound?
- Are there species specific differences in these parameters?
- Are there differences between pathological and physiological conditions?
- Can we simulate and predict PK parameters regardless which species, administration route, and dose we are looking at?
Further downstream in the drug discovery and development process we assess the primary pharmacodynamic effects of a compound (PD: studies on the mode of action and/or effects of a substance in relation to its desired therapeutic target). To address this question we are using:
- Simple PK-PD models to check dose-response efficacy on limited, but relevant pathological signs
- A suitable target disease animal model to treat with compound prophylactically or therapeutically
- A combination of in vitro potency across species, PK simulations and allometric scaling to predict suitable dose for the specific route of administration and plasma level in different species including humans
- Appropriate read-outs / markers to quantify the efficacy of the compound
Additionally and if necessary, Polyphor can also perform in collaboration with CROs:
Secondary pharmacodynamic studies on the mode of action and/or effects of a substance not related to its desired therapeutic target.
Safety pharmacology studies to identify adverse pharmacodynamic effects.