In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches

Isabel Lozoya-Agullo, Moran Zur, Omri Wolk, Avital Beig, Isabel González-Álvarez, Marta González-Álvarez, Matilde Merino-Sanjuán, Marival Bermejo, Arik Dahan

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Intestinal drug permeability has been recognized as a critical determinant of the fraction dose absorbed, with direct influence on bioavailability, bioequivalence and biowaiver. The purpose of this research was to compare intestinal permeability values obtained by two different intestinal rat perfusion methods: the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop) rat perfusion method. A list of 15 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was constructed. We assessed the rat intestinal permeability of these 15 model drugs in both SPIP and the Doluisio methods, and evaluated the correlation between them. We then evaluated the ability of each of these methods to predict the fraction dose absorbed (Fabs) in humans, and to assign the correct BCS permeability class membership. Excellent correlation was obtained between the two experimental methods (r2 = 0.93). An excellent correlation was also shown between literature Fabs values and the predictions made by both rat perfusion techniques. Similar BCS permeability class membership was designated by literature data and by both SPIP and Doluisio methods for all compounds. In conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method are both equally useful for obtaining intestinal permeability values that can be used for Fabs prediction and BCS classification.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume480
Issue number1-2
DOIs
StatePublished - 1 Mar 2015

Keywords

  • Bioequivalence
  • Biopharmaceutics classification system
  • Biowaiver
  • Intestinal permeability
  • Oral drug absorption
  • Perfusion study

ASJC Scopus subject areas

  • Pharmaceutical Science

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