Pharmacokinetic studies in Netherlands

The attrition of drug candidates during the long process of drug discovery and development is the issue that is faced by the pharmaceutical industry today. Attrition problem adversely affects the R and D cost of the drug and delivery to the clinic. 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. In order to achieve this it is important to understand the root causes of attrition that have led to drug development failure in the past. 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. Today, Pharmacokinetic studies determine the success or failure of a drug with emphasis on cost, speed and 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. Pharmacokinetics provides a mathematical basis to assess the time course of drugs and their effects in the b Pharmacokinetic studies in Netherlands ody. It enables the following processes to be quantified: Absorption, Distribution, Metabolism, and Excretion. These four processes together are called as ADME. These factors are particularly important in the case of assessment of risk in NCEs. The undesired PK characteristics include 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. Hence, In vivo pharmacokinetic (PK) screening can be instrumental in the selection of lead compounds with desirable bioavailability profiles for further investigation in 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. The above said aspects can be partially addressed by correlating it with pharmacodynamics 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. It is observed that such relationships are very complex. We see that such relationships are really complex. So, it is important that we design preclinical models that will provide information about mechanistically relevant PK/PD models. A data becomes more available, the initial models can be refined further. A predictive tool that can have an in-depth understanding about the efficacy requirements is the ultimate output that we get from this exercise. 

A well designed PK/PD will offer logical approach to understand the mechanism of action of drug and select the most optimal approach. Application of PK/PD modelling in the early discovery can minimise the animal usage and predict the dosage range right from early clinical testing. Integration of data from different studies in a sequential manner is made possible with the PK-PD models. As the result of the above said reasons, PK and PD are becoming more and more important in the drug R and D.