Baishakhi De, Koushik Bhandari, Ranjan Mukherjee, Prakash Katakam, Shanta K. Adiki, Rohit Gundamaraju and Analava Mitra* Pages 142 - 155 ( 14 )
Background: The world has witnessed growing complexities in disease scenario influenced by the drastic changes in host-pathogen- environment triadic relation. Pharmaceutical R&Ds are in constant search of novel therapeutic entities to hasten transition of drug molecules from lab bench to patient bedside. Extensive animal studies and human pharmacokinetics are still the “gold standard” in investigational new drug research and bio-equivalency studies. Apart from cost, time and ethical issues on animal experimentation, burning questions arise relating to ecological disturbances, environmental hazards and biodiversity issues. Grave concerns arises when the adverse outcomes of continued studies on one particular disease on environment gives rise to several other pathogenic agents finally complicating the total scenario. Thus Pharma R&Ds face a challenge to develop bio-waiver protocols. Lead optimization, drug candidate selection with favorable pharmacokinetics and pharmacodynamics, toxicity assessment are vital steps in drug development.Methods: Simulation tools like Gastro Plus™, PK Sim®, SimCyp find applications for the purpose. Advanced technologies like organ-on-a chip or human-on-a chip where a 3D representation of human organs and systems can mimic the related processes and activities, thereby linking them to major features of human biology can be successfully incorporated in the drug development tool box. Results: PBPK provides the State of Art to serve as an optional of animal experimentation. PBPK models can successfully bypass bio-equivalency studies, predict bioavailability, drug interactions and on hyphenation with in vitro-in vivo correlation can be extrapolated to humans thus serving as bio-waiver. Conclusion: PBPK can serve as an eco-friendly bio-waiver predictive tool in drug development.
Therapeutic entities, Lead optimization, bio-equivalency, bio-waiver, biodiversity pharmacokinetics, pharmacodynamics, human-on-a chip.
School of Medical Science & Technology, IIT Kharagpur, 721302, West Bangal, School of Medical Science & Technology, IIT Kharagpur, 721302, West Bangal, School of Medical Science & Technology, IIT Kharagpur, 721302, West Bangal, Priyadarshini Institute of Pharmaceutical Education and Research, Guntur, AP, Nirmala College of Pharmacy, Guntur 522503, Andhra Pradesh, School of Health Sciences, University of Tasmania, Launceston, Tasmania, School of Medical Science and Technology, IIT Kharagpur, 721302, West Bangal