Mechanistic and Conventional IVIVC: Complementary or Clashing Approaches?

Drug developers frequently use in vitro-in vivo correlations (IVIVCs) to:

  • Serve as a surrogate for human bioequivalence (BE) studies.
  • Support and/or validate the use of dissolution methods and specifications.
  • Assist in quality control during manufacturing and selecting appropriate formulations.

Conventional IVIVC uses deconvolution methods such as Wagner Nelson, Loo-Riegelman and numerical deconvolution to estimate the rate of input of drug into the systemic circulation from observed plasma drug concentrations of the oral formulation with the use of the unit impulse response (UIR). Clearly, there have been many instances of successful development and use of conventional IVIVC models. However, there are also cases where conventional models are not useful for developing correlations.

Physiologically-based pharmacokinetic (PBPK), mechanistic IVIVC is an emerging approach that separately accounts for the multiple mechanisms that determine a drug’s in vivo input rate considering transit time, gut wall permeability, gut wall metabolism, and hepatic first-pass metabolism from dissolution rate. In this webinar, Venkateswari Muthukrishnan and Nikunjkumar Patel presented a case study that illustrates the differences between conventional and mechanistic IVIVC and provide guidance on tools that support each approach.

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