Outsourcing pharmacokinetic studies

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. In order to achieve this it is important to understand the root causes of attrition that have led to drug development failure in the past. The attrition happens at the level of animal testing for toxicity where the safely issues play an important role Pharmacokinetic profile of the compound is important factor in the assessment of the safety of these compounds. 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 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 are usually called as ADME These factors are particularly important in the case of assessment of risk in 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 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.

This kind of increased emphasis on the PK profile has led to reduction in the termination of programs due to pharmacokinetic profile issues. This in turn has highlighted the other causes for compounds being considered unsuitable for drug development. Such reasons include inadequate safety and efficacy. The above said aspects can be partially addressed by correlating it with pharmacodynamics 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 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. The studies are designed with the basic assumptions of understanding relationship between the exposure of the medication and associated therapeutic activ outsourcing pharmacokinetic studies ity. Such relationships are generally 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. 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. Allocation of PK/PD modelling in the development programs ca help in minimization of in vivo models in the later phase and predict the dosage ranges for early clinical testing. Integration of data from different studies in a sequential manner is made possible with the PK-PD models. So, Pharmacokinetics and Pharmacodynamics are becoming increasingly important in the drug discovery process.