Pharmacokinetic studies in Spain

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 candidate without the expected qualities will help in reduction of the overall cost of drug R and D. This approach has been proven effective by multiple studies. 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. A factor in the assessment of safety during early drug development is the pharmacokinetic profile of the compound. Pharmacokinetic studies have become the most important factor in determining the success of the drug due to its impact on the cost and ability to predict the drug properties with great levels of 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. 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. The resultant PK screening can be instrumental in selection of lead compounds when with the wanted bioavailability characteristics and will help in the further 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 in turn has highlighted the other causes for compounds being considered unsuitable for drug development. Such reasons include inadequate safety and efficacy.  Both of these aspects can be partially addressed by extending the prediction of pharmacokinetic behaviour to include the pharmacodynamic 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.

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. We build the study designs with an assumption to study the relationship between medical exposure and therapeutic activity. It is observed that such relationships are very comp Pharmacokinetic studies in Spain lex. We see that such relationships are really complex. So, it is important that we design preclinical models that will provide information about mechanistically relevant PK/PD models. A data becomes more available, the initial models can be refined further. 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. 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.