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Mechanistic and Conventional IVIVC: Complementary or Clashing Approaches?

On-Demand Webinar

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, Dr Venkateswari Muthukrishnan and Dr Nikunjkumar Patel presented a case study that illustrates the differences between conventional and mechanistic IVIVC and provide guidance on tools that support each approach.

About Our Speakers

Venkateswari Muthukrishnan, Senior Scientific Consultant, Certara. Dr. Venkateswari Muthukrishnan joined Certara in 2012. She is responsible for Training and Pre-sales Support in South Asia Pacific and Middle East. In addition, she provides Training and Support on Phoenix Products: Phoenix WinNonlin, NLME, Connect and IVIVC Toolkit. Prior to joining Certara, she held positions at a number of organizations including: AAI International, FibroGen Inc., Biocon Limited, Nektar Therapeutics India Pvt. Ltd., PharMantra Consulting Services, and BITS-Pilani (HYD).

Nikunjkumar Patel, Senior research scientist, Certara. Dr. Nikunj Patel is a senior research scientist in Certara’s modeling and simulations group where he is leading oral and dermal absorption projects and is a member of the Cardiac Safety Simulator development team. He joined Certara in August 2011 and led the development of the physiologically based IVIVC (PB-IVIVC) module of the Simcyp Simulator and the Pharmaceutics module of SIVA (Simcyp In Vitro (data) Analysis) platform. Before joining Certara, he spent three years at the life science innovation labs of Tata Consultancy Services as a research scientist mainly working on pharmacokinetic/pharmacodynamic modeling and QSAR development for various ADMET properties. During his graduate studies, he used computer aided drug design (CADD) and molecular modeling to identify safe and potent novel anti-diabetic ligands.

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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