Pharmacokinetic services

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. 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. During the in Vivo toxicity testing, major percentage of attrition happens owing to the safely issues. Pharmacokinetic profile of the compound is important factor in the assessment of the safety of these compounds. PK studies now help in determining the success of the drug with ability to accurately predict the drug properties and also curtail the costs of 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 provides a mathematical basis to assess the time course of drugs and their effects in the body. It enables the following processes to be quantified: Absorption, Distribution, Metabolism, and Excretion. 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. Many tools have been developed for predicting drug absorption, drug clearance and drug-drug interaction. Along with this PK parameters from animals to man have also been introduced. 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.

This kind of increased emphasis on the PK profile has led to reduction in the termination of programs due to pharmacokinetic profile issues. In turn this has shifted the focus on other compounds being considered unsuitable for drug development. Safety and Efficacy are such reasons. 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.

Detailing the relationship between the PK and PD is a critical factor for the development of new drugs. 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. Rational study design is based on the assumption of a causal relationship between exposure to a medication and its therapeutic activ pharmacokinetic services ity. Such relationships are generally 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. A data becomes more available, the initial models can be refined further. The ultimate output is a powerful predictive tool based on an in-depth understanding of the requirements for efficacy.

Well planned PK/PD study offers a rational approach to the efficient and informative drug development. This will help the teams in understanding the mechanism of action of a drug. Thus helping us to select the most optimal drug. 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. PK/PD models allow integration of data from different studies in a logical manner based on the understanding of drug and disease. As a result of the above said factors, PK and PD studies are becoming more important in R and D.