Exploratory PK & Toxicity Studies

Pharmacodynamics (PD) refers to the action of a drug to the body, involving receptor binding, post-receptor effects, and chemical interactions. Pharmacokinetics (PK) determines the onset, duration, and intensity of drug action. Successful drug discovery relies on the selection of drug candidates with good in vivo PK properties, as well as appropriate preclinical efficacy and safety. In vivo PK profiling is often a bottleneck in the discovery process.

In order to prove effective, a drug delivered to the patient must reach the necessary concentration in the plasma and in relevant tissues (as measured by PK). This is necessary to effectively modulate the activity of the target protein (as measured by PD) in the body. Incorporating in vivo PK/PD efficacy studies at the early stages of drug development program can significantly accelerate the selection of the most promising compounds. The rationales for conducting in vivo PK/PD efficacy studies in preclinical models are to:

provide a quantitative analysis of the dose-response relationships;
describe and predict the time-course effects of one or multiple drug doses;
understand the frequency and the extent of target modulation to observe statistically significant efficacy;
determine efficacious dosing regimens with an acceptable therapeutic index.

PK/PD analysis is typically performed at every stage of the drug development process. As development is becoming more complex, time consuming, and cost intensive, Creative bioarray is looking to make better use of PK/PD data to eliminate defective candidates from the outset and identify those most likely to achieve clinical success.