Pharmacokinetic studies in Netherlands
The problem faced by pharmaceutical companies is the drug candidate attrition throughout the drug discovery and development process. This problem significantly increases the cost and delays the launch of product in the market. If the drug development program that will fail can be identified very early in the drug discovery and abandoned, the overall drug development costs will significantly decrease. For abandoning the possible failure candidate, it is important to understand the factors that have contributed to the failure of the products in the past. A significant cause of attrition is due to safety issues arising as a result of animal toxicity testing. A factor in the assessment of safety during early drug development is the pharmacokinetic profile of the compound. Pharmacokinetic studies have become the most important factor in determining the success of the drug due to its impact on the cost and ability to predict the drug properties with great levels of accuracy.
Pharmacokinetics has evolved over the past two decades to become an integral part of the drug development process especially in identifying a drug’s biological properties. PK provides the mathematical basis for understanding the absorption, biodistribution, metabolism of the drug and elimination of it from the body. These four processes are usually 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. There is a lot of development in 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.
There has been a rise in consideration of suitability of the PK profile of the drug candidate. This has led to the decrease in the early termination of the programs due to pharmacokinetic failings. This resulted in the emphasis on other causes for compounds being considered unsuitable for drug development like safety and efficacy. These aspects can be addressed by understanding the complete pharmacokinetic behaviour along with pharmacodynamics profile of the drug candidate. Pharmacodynamic studies along with identification of suitable biomarkers pertaining to the safety and efficacy help in the safety profiling the drug candidate.
Drawing inferences from the correlation between the Pharacokinetics and Pharmacokinetics is an important tool that is emerging. Also, the PK/PD modelling can help in increasing the conversion rates from in vitro to in vivo to further these findings in preclinical and clinical settings. Rational study design is based on the assumption of a causal relationship between exposure to a medication and its therapeutic activity. It is observed that such relationships are very complex. We see that such relationships are really complex. So, we have to develop a dynamic preclinical studies model that will provide information to build a mathematical and mechanistically relevant PK/PD models. Pharmacokinetic studies in Netherlands As data becomes available, initial models can be refined through an iterative process. 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 testing. PK-PD models help in the aggregation of data from various studies and help in deeper understanding of relationship between drug and the disease. So, Pharmacokinetics and Pharmacodynamics are becoming increasingly important in the drug discovery process.
