Pharmacokinetics outsourcing

The challenge faced by the bio-pharmaceutical industry is the attrition that the drug candidates face over the course of drug discovery and development. When he timelines gets prolonged and the costs shoot-up, due to the attrition, public health gets affected. The problem often results in the concerns about the public health and safety if the costs and timelines of drug discovery are extended. 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. The attrition happens at the level of animal testing for toxicity where the safely issues play an important role 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.

Over the last few years, Pharmacokinetics has emerged as an integral part of drug development, especially when 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 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. 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. As we see the resultant PK screening results can be used in the selecting a lead compound with desired bioavailability profile. This information can be used in furthering the drug discovery 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 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 PD studies and the safety and efficacy biomarkers provide depth of data and help in assessment of safety of the drug candidates.

Characterizing the relationship between the pharmacokinetics (PK, concentration vs. time) and pharmacodynamics (PD, effect Pharmacokinetics outsourcing  vs. time) is an important tool in the discovery and 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. 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. Based on the data from these models, we can further refine the basic models of study. A predictive tool that can have an in-depth understanding about the efficacy requirements is the ultimate output that we get from this exercise. 

A well designed PK/PD will offer logical approach to understand the mechanism of action of drug and select the most optimal approach. 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. So, Pharmacokinetics and Pharmacodynamics are becoming increasingly important in the drug discovery process.