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    Multi-Segmental Evaluation of Intestinal Permeability of Amlodipine at Two Dose Levels
    (Bentham Science Publ Ltd, 2025) Ates, Muge; Stelmasinska, Agata Bogacz; Stelmasinska, Michal; Barre, Liban; Buyuktuncel, Ebru; Kaynak, Mustafa Sinan; Sahin, Selma
    Background Intestinal permeability plays a crucial role in drug absorption, as it varies across different gastrointestinal regions, affecting the bioavailability of orally administered drugs. This variability, combined with dose-dependent absorption, influences the overall efficacy and pharmacokinetics of the drug.Objective This study aimed to investigate the impact of three intestinal regions (jejunum, ileum, and colon) along with two different doses of amlodipine (AML) (5 mg and 10 mg) on its permeability.Methods An optimized HPLC method was developed and validated for the simultaneous quantification of AML, metoprolol (MTP), and phenol red (PR), while a modified single-pass intestinal perfusion (SPIP) was used to assess AML permeability across different intestinal segments.Results Net Water Flux (NWF) showed significant fluctuations, with high positive values in the colon, indicating distinct physiological responses in this region. The effective permeability (Peff) of AML varied across different intestinal segments and doses. In the jejunum and ileum, the Peff of AML decreased with increasing doses from 5 mg to 10 mg, while in the colon, Peff remained relatively stable. Peff values ranged from 3.50 x 10-4 cm/s for the 5 mg dose to 1.80 x 10-4 cm/s for the 10 mg dose in the jejunum, from 3.30 x 10-4 cm/s (5 mg) to 2.41 x 10-4 cm/s (10 mg) in the ileum, and from 6.65 x 10-4 cm/s (5 mg) to 6.79 x 10-4 cm/s (10 mg) in the colon.Conclusion This study demonstrated significant segmental and dose-dependent variations in the intestinal permeability of AML using the SPIP model in rats.