title: Drug gastrointestinal absorption in rat: Strain and gender differences.
abstract: Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only CD∗IGS and Wistar Unilever showed differences between males and females. For Verapamil, Wistar Han and Sprague-Dawley strains do not show differences between male and female rats. That means that in these strains permeability data from male and female could be combined. In male rats, which are commonly used for permeability estimation, there were differences for Metoprolol permeability between Sprague-Dawley (with lower permeability values) and the other strains, while for Verapamil Sprague-Dawley and Wistar-Han showed the lower permeability values. In conclusion, the selection of rat's strain and gender for intestinal absorption experiments is a relevant element during study design and data from different strains may not be always comparable.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Valencia, Spain.
authors.forename: Davinia
authors.initials: D
authors.lastname: Oltra-Noguera
authors.affiliation: Department of Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Faculty of Pharmacy, Miguel Hernandez University, Elche, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Mangas-Sanjuan
authors.affiliation: Department of Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Faculty of Pharmacy, Miguel Hernandez University, Elche, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: González-Álvarez
authors.affiliation: Department of Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Faculty of Pharmacy, Miguel Hernandez University, Elche, Spain; Analysis and Control Department, University of Los Andes, Venezuela.
authors.forename: Sarin
authors.initials: S
authors.lastname: Colon-Useche
authors.affiliation: Department of Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Faculty of Pharmacy, Miguel Hernandez University, Elche, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: González-Álvarez
authors.affiliation: Department of Engineering: Pharmacokinetics and Pharmaceutical Technology Area, Faculty of Pharmacy, Miguel Hernandez University, Elche, Spain. Electronic address: mbermejo@goumh.umh.es.
authors.forename: Marival
authors.initials: M
authors.lastname: Bermejo
mesh_terms: D000818:Animals; D005260:Female; D007408:Intestinal Absorption; D008297:Male; D008790:Metoprolol / Q000378:metabolism*; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012727:Sex Characteristics; D013045:Species Specificity; D014700:Verapamil / Q000378:metabolism*
chemical_list: D014700:Verapamil; D008790:Metoprolol
keywords: Gender; In situ; Intestinal permeability; Strain; Variability