Pharmacokinetic studies in Netherlands

Attrition of drug candidates over the course of drug discovery process if the biggest threat plaguing the biopharmaceutical industry. The cost and timelines are adversely affected creating loss to the companies and huge impact on the quality of life at large. An early termination of a drug development program that will fail will help pharmaceutical companies in reducing the overall cost of R and D. Understanding of the reasons that contributed to the previous drug failures is required for identifying the possible candidate that will fail. A significant cause of attrition is due to safety issues arising as a result of animal toxicity testing. The PK profile of the compound is an important factor to determine the safety during the early stages of drug development. In the current atmosphere of drug R and D, PK studies play an important role in determining the success or failure of the drug. It also helps us control the cost and pace of the research.

Pharmacokinetics has become an intricate part of the drug discovery process. It is particularly useful for finding out the biological properties of the Drug. PK studies help in determination of drug absorption, distribution and how it gets excreted from the body and what it becomes over this journey. These four processes together are called as ADME. These factors become critical in the case of assessing risk in a new chemical entity often abbreviated as NCEs. Undesired PK behaviour includes factors such as low bioavailability due to high extraction or poor absorption characteristics, short elimination half-life leading to short duration of action and excessive variability due to genetic or environmental factors. Much progress has been made in developing tools for the prediction of drug absorption, drug clearance and drug–drug interactions, in addition to the scaling of pharmacokinetic parameters from animals to man. The resultant PK screening can be instrumental in selection of lead compounds when with the wanted bioavailability characteristics and will help in the further drug development programs.

This increased consideration of the suitability of the pharmacokinetic profile has led to a reduction in the early termination of programmes due to pharmacokinetic failings. In turn this has shifted the focus on other compounds being considered unsuitable for drug development. Safety and Efficacy are such reasons. These aspects can be addressed by understanding the complete pharmacokinetic behaviour along with pharmacodynamics profile of the drug candidate. Preclinical pharmacodynamics studies and the identification of appropriate safety and efficacy biomarkers provide avenues to increase the confidence in rationale and safety of new drug molecules.

Drawing inferences from the correlation between the Pharacokinetics and Pharmacokinetics is an important tool that is emerging. Additionally, PK/PD modeling can help increase the translation of in vitro compound potency to the in vivo setting, reduce the number of in vivo animal studies, and improve translation of findings from preclinical species into the clinical setting. The studies are designed with the basic assumptions of understanding relationship between the exposure of the medication and associated therapeutic activity. Such relationships are usually very complex. So, it is important that we design preclinical models that will provide information about mechanistically relevant PK/PD models. Based on the data from these models, we can further refine the basic models of study. The ultimate output is a powerful predictive tool based on an in-depth understanding of the requirements for efficacy.

A well designed PK/PD study offers a rational approach to efficient and informative drug development and can help the project team to understand the mechanism of action of a drug and select the optimal compound. Allocation of PK/PD modelling in the development programs ca help in minimization of in vivo models in the later phase and predict the dosage ranges for early clinical Pharmacokinetic studies in Netherlands testing. Integration of data from different studies in a sequential manner is made possible with the PK-PD models. So, Pharmacokinetics and Pharmacodynamics are becoming increasingly important in the drug discovery process.