Pharmacokinetic services

The challenge faced by the bio-pharmaceutical industry is the attrition that the drug candidates face over the course of drug discovery and development. 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. Understanding of the reasons that contributed to the previous drug failures is required for identifying the possible candidate that will fail. During the in Vivo toxicity testing, major percentage of attrition happens owing to the safely issues. 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 body. It enables the following processes to be quantified: Absorption, Distribution, Metabolism, and Excretion. These four processes together are called 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. 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. 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 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 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 dr pharmacokinetic services ugs. 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 activity. Such relationships are usually very 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. Based on the data from these models, we can further refine the basic models of study. The ultimate output is a powerful predictive tool based on an in-depth understanding of the requirements for efficacy.

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. 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.