PK studies in beagle dogs

The biggest problem that is plaguing the pharmaceutical industry is the attrition of drug candidates over the process 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. Early termination of drug development programmes that will ultimately fail is seen as an approach that leads to overall cost reduction. 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. PK studies in beagle dogs  The attrition happens at the level of animal testing for toxicity where the safely issues play an important role A factor in the assessment of safety during early drug development is the pharmacokinetic profile of the compound. 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.

Over the last few years, Pharmacokinetics has emerged as an integral part of drug development, especially when identifying a drug’s biological properties. PK provides the mathematical basis for understanding the absorption, biodistribution, metabolism of the drug and elimination of it from the body. These four processes are usually 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. 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. 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 resulted in the emphasis on other causes for compounds being considered unsuitable for drug development like 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. Pharmacodynamic studies along with identification of suitable biomarkers pertaining to the safety and efficacy help in the safety profiling the drug candidate.

Drawing inferences from the correlation between the Pharacokinetics and Pharmacokinetics is an important tool that is emerging. 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. 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. As data becomes available, initial models can be refined through an iterative process. A predictive tool based on the understanding of the requirements for efficacy is the final output from this work.

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 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.