Pharmacokinetics CRO

The biggest problem that is plaguing the pharmaceutical industry is the attrition of drug candidates over the process of drug discovery and development. 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. An understanding of the reasons that contributed to the drug development failures is important for determining which drug candidate will fail. 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. Today, Pharmacokinetic studies determine the success or failure of a drug with emphasis on cost, speed and accuracy. pharmacokinetics CRO 

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 provides the mathematical basis for understanding the absorption, biodistribution, metabolism of the drug and elimination of it from the body. These pharmacokinetic processes often referred to as ADME  determine the drug concentration in the body when medicines are prescribed. These are abbreviated as ADME. This is particularly applicable when assessing the risk of a new chemical entity (NCE) in relation to safety parameters such as QT interval prolongation, where free plasma concentrations have been shown to be predictive of this property in relation to potency in preclinical testing. Inappropriate pharmacokinetic behaviour includes such factors 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. 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. 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.

Detailing the relationship between the PK and PD is a critical factor for the development of new drugs. PK/PD modeling can also help in translating the in vitro compound potency from all the way from in vitro setting to clinical phases. We build the study designs with an assumption to study the relationship between medical exposure and 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. Based on the data from these models, we can further refine the basic models of study. 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. 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 a result of the above said factors, PK and PD studies are becoming more important in R and D.