title: In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches.
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 (r(2)=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.
authors.affiliation: Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain; Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lozoya-Agullo
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Zur
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Wolk
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Beig
authors.affiliation: Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Álvarez
authors.affiliation: Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: González-Álvarez
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain; Molecular Recognition and Technological Development, Polytechnic University, University of Valencia, Valencia, Spain.
authors.forename: Matilde
authors.initials: M
authors.lastname: Merino-Sanjuán
authors.affiliation: Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain.
authors.forename: Marival
authors.initials: M
authors.lastname: Bermejo
authors.affiliation: Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: arikd@bgu.ac.il.
authors.forename: Arik
authors.initials: A
authors.lastname: Dahan
mesh_terms: D000818:Animals; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010477:Perfusion / Q000379:methods; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000145:classification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004364:Pharmaceutical Preparations
keywords: Bioequivalence; Biopharmaceutics classification system; Biowaiver; Intestinal permeability; Oral drug absorption; Perfusion study