Pharmacokinetics outsourcing908

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. The cost and timelines are adversely affected creating loss to the companies and huge impact on the quality of life at large. 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 major reason for this attrition is the safety issues that arise during the animal toxicity testing. A factor in the assessment of safety during early drug development is the pharmacokinetic profile of the compound. 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 jour Pharmacokinetics outsourcing ney. These pharmacokinetic processes often referred to as ADME  determine the drug concentration in the body when medicines are prescribed. These are abbreviated as ADME. These factors become critical in the case of assessing risk in a new chemical entity often abbreviated as NCEs. 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. As a result, PK screening is instrumental in selection of lead compounds with the expected bioavailability profiles for taking the drug discovery process further.

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. This in turn has highlighted the other causes for compounds being considered unsuitable for drug development. Such reasons include inadequate 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. 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. Such relationships are generally complex. So, it is important that we design preclinical models that will provide information about mechanistically relevant PK/PD models. As data becomes available, initial models can be refined through an iterative process. A predictive tool based on the understanding of the requirements for efficacy is the final output from this work.

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. Applying PK/PD modelling in early discovery and development programs can minimize animal usage, shorten the development time, estimate the therapeutic index, and predict the dose ranges in 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.