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Bioavailability and Bioequivalence: Focus on Physiological Factors and Variability

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Abstract

This is a summary report of the EUFEPS & COST B25 conference on Bioavailability and Bioequivalence which focused on physiological factors and variability. This conference was held at The Royal Olympic Hotel in the centre of Athens (Greece) during the 1–2 of October in 2007. The issues discussed in the conference involved physiological factors affecting drug absorption, the role of pre-systemic effects on bioavailability (BA), the impact of variability in bioequivalence (BE) studies, and a final closing panel session on unresolved issues in BA/BE regulations. Several important aspects of drug absorption were highlighted. It was presented how the complexity of gastrointestinal (GI) physiology and the site dependent absorption can impact on drug BA. Similarly, the effects of food and formulation were also studied. The second session focused on integrating the complexities of GI into modeling the inter-individual variability of absorption and the prediction of first-pass metabolism from in-vitro data. The necessity to measure metabolites, the value of Biopharmaceutical Classification System (BCS), and the more recently proposed Biopharmaceutical Drug Disposition Classification System (BDDCS) were assessed as well. This session closed with presentations of pharmacokinetic software delegates. In the second day of the conference, the problem of high intra-subject variability in BE studies was analyzed. Study design considerations, the use of multiple-dose studies and the role of statistics in BE were also highlighted. Finally, the current thinking of regulatory authorities (EMEA and US-FDA) was presented. The conference closed with a last session on unresolved issues in the regulatory level.

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Authors and Affiliations

  1. Department of Pharmacy, University of Athens, Athens, Greece

    Vangelis Karalis & Panos Macheras

  2. Johnson & Johnson, Beerse, Belgium

    Achiel Van Peer

  3. International Pharmaceutical Federation, North Potomac, Maryland, USA

    Vinod P. Shah

Authors
  1. Vangelis Karalis
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  2. Panos Macheras
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  3. Achiel Van Peer
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  4. Vinod P. Shah
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Correspondence to Vinod P. Shah.

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Contributors

Jose A. Morais, University of Lisbon, Lisbon, Portugal

Victor A. Voicu, Romanian Academy and University of Medicine and Pharmacy

Carol Davila, Bucharest

Clive G. Wilson, Strathclyde Institute for Pharmacy and Biomedical Sciences, Glasgow, Scotland UK

Thomas Gramatte, Munich, Germany

Frank Donath, SocraTec R&D, Oberursel, Germany.

Werner Weitschies, University of Greifswald, Greifswald, Germany

Sigrid Stockbroekx, Johnson & Johnson, Beerse, Belgium

Constantin Mircioiu, University of Medicine and Pharmacy, Bucharest, Romania Amin Rostami-Hodjegan, University of Sheffield and Simcyp Ltd, Sheffield, UK Henning H. Blume, SocraTec R&D, Oberursel, Germany.

Geoffrey T. Tucker, University of Sheffield, Sheffield, UK

Leslie Z. Benet, University of California, San Francisco, CA, USA Meir Bialer, Hebrew University of Jerusalem, Jerusalem

Kamal K. Midha, University of Saskatchewan and Pharmalytics Inc, Saskatoon, Canada.

Tomas Salmonson, Medical Products Agency, Uppsala, Sweden

Barbara M. Davit, FDA, Rockville, MD, USA

George Aislaitner, National Organisation for Medicines, Athens, Greece

Alfredo Garcia-Arieta, Spanish Agency for Medicines and Health Care Products, Madrid, Spain.

Jan Welink, Medicines Evaluation Board, The Hague, Netherlands.

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Karalis, V., Macheras, P., Van Peer, A. et al. Bioavailability and Bioequivalence: Focus on Physiological Factors and Variability. Pharm Res 25, 1956–1962 (2008). https://doi.org/10.1007/s11095-008-9645-9

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