Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat perfusion.
Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was assessed in three small intestinal regions: the upper jejunum, mid-small intestine, and the terminal ileum, using both the SPIP and the Doluisio experimental methods. Excellent correlation was evident between the two approaches, especially in the upper jejunum (R2=0.95). Significant regional-dependent permeability was found in half of drugs studied, illustrating the importance and relevance of segmental-dependent intestinal permeability. Despite the differences between the two methods, highly comparable results were obtained by both methods, especially in the medium-high Peffrange. In conclusion, the SPIP and the Doluisio method are both equally useful in obtaining crucial segmental-dependent intestinal permeability data.
Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain; Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain.
Isabel
I
Lozoya-Agullo
Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Moran
M
Zur
Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Avital
A
Beig
Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Noa
N
Fine
Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Yael
Y
Cohen
Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain.
Marta
M
González-Álvarez
Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain; Molecular Recognition and Technological Development, Polytechnic University-University of Valencia, Valencia, Spain.
Matilde
M
Merino-Sanjuán
Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain.
Isabel
I
González-Álvarez
Department of Engineering, Pharmacy Section, Miguel Hernandez University, Alicante, Spain.
Marival
M
Bermejo
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.
Arik
A
Dahan
D000284:Administration, Oral; D000818:Animals; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004364:Pharmaceutical Preparations
Biopharmaceutics classification system; Intestinal permeability; Oral drug absorption; Segmental-dependent permeability