Drug discovery and development is a complex, time consuming and expensive process. It has been estimated that approximately 50% of drugs fail in phase II clinical development.
The integration of Pharmacokinetics (PK) and Pharmacodynamics (PD) along with utilization of novel biomarkers/surrogate markers from early to late stage of drug discovery can guide the decision making process on lead generation, optimization, safety assessment, PK/PD evaluation and product realization. PK/PD studies help demonstrate a mechanism and to obtain rough quantitative information on the link between the dose and the effect of the drug.
The Modeling and Simulation (M&S) group at Piramal Healthcare contributes in the drug discovery efforts by performing:
- PK/PD analysis of both non-clinical and clinical studies
- First in human (FIH) dose predictions based on allometric scaling, efficacy, biomarker and safety data to provide guidance to the clinicians in designing the future clinical trials.
- Routine compartmental and non-compartmental PK analysis, protocol and report writing
- Population PK/PD analysis.
Pharmacometrics, an emerging field is defined as the science that quantifies drug, disease, and trial information to aid efficient drug development and/or regulatory decisions. Pharmacometric models describe the relationship between exposure (PK) and response (PD) for both desired and undesired effects, and individual patient characteristics.
The model based drug development (MBDD) approach applied at the Piramal Research Centre helps to:
- Decrease drug development time & cost
- Rationalize selection of optimized dosage regimens for human clinical trials
- Estimate and account for potentially large inter-patient variability
- Understand the benefits of different dosing intervals and difference of investigational product formulations
- Test and account for influential covariate effects such as baseline, age, sex or other parameters;
- Integrate data from various species and translate from animal to man
- Individualize the dosage regimen of an individual patient using Bayesian methods
- Validate the proposed optimal study design by simulating clinical trials.
The M&S group utilizes different software for the PK/PD modeling and simulations such as Phoenix (WinNonlin version 6.1), R and NONMEM version 7.