Pharmacokinetic studies in USA
The problem faced by pharmaceutical companies is the drug candidate attrition throughout the drug discovery and development process. 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. 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. 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. Pharmacokinetic studies in USA
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 become critical in the case of assessing risk in a new chemical entity often abbreviated as NCEs. Undesired PK behaviour includes factors such 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 kind of increased emphasis on the PK profile has led to reduction in the termination of programs due to pharmacokinetic profile issues. 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. 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.
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. 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. The studies are designed with the basic assumptions of understanding relationship between the exposure of the medication and associated therapeutic activity. Such relationships are generally 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. 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.
Well planned PK/PD study offers a rational approach to the efficient and informative drug development. This will help the teams in understanding the mechanism of action of a drug. Thus helping us to select the most optimal drug. Application of PK/PD modelling in the early discovery can minimise the animal usage and predict the dosage range right from early clinical testing. Integration of data from different studies in a sequential manner is made possible with the PK-PD models. As a result of the above said factors, PK and PD studies are becoming more important in R and D.
