Pharmacokinetic studies in India
The problem faced by pharmaceutical companies is the drug candidate attrition throughout the drug discovery and development process. This problem significantly increases the cost and delays the launch of product in the market. 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 A factor in the assessment of safety during early drug development is the pharmacokinetic profile of the compound. Today, Pharmacokinetic studies determine the success or failure of a drug with emphasis on cost, speed and 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. PK studies help in determination of drug absorption, distribution and how it gets excreted from the body and what it becomes over this journey. 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 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. 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 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 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. Pharmacokinetic studies in India 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.
