CRO for PK studies

Attrition of drug candidates over the course of drug discovery process if the biggest threat plaguing the biopharmaceutical industry. This problem going to increase the cost of drugs and also increase timelines for introduction to market. An early termination of a drug development program that will fail will help pharmaceutical companies in reducing the overall cost of R and D. 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 major reason for this attrition is the safety issues that arise during the animal toxicity testing. Pharmacokinetic profile of the compound is important factor in the assessment of the safety of these compounds. 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 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 (PK) is dedicated to determining the mechanisms of a drug’s absorption, biodistribution, when it eliminated from the body and what it becomes. It is a study of how an organism affects a drug. 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. 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 CRO for PK studies  to man. As a result, PK screening is instrumental in selection of lead compounds with the expected bioavailability profiles for taking the drug discovery process further.

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. We build the study designs with an assumption to study the relationship between medical exposure and therapeutic activity. Such relationships are generally complex. Therefore it is important to design robust preclinical studies that will provide information to build mechanistically relevant PK/PD mathematical models. A data becomes more available, the initial models can be refined further. A predictive tool based on the understanding of the requirements for efficacy is the final output from this work.

A well designed PK/PD will offer logical approach to understand the mechanism of action of drug and select the most optimal approach. 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.