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
be extrapolated to humans thus serving as bio-waiver.
Conclusion: PBPK can serve as an eco-friendly bio-waiver predictive tool in drug