Canine Mdr1 Knockout MDCK Cells Reliably Estimate Human Small Intestinal Permeability (<i>P</i>_eff) and Fraction Absorbed (<i>f</i>_a).

ABSTRACT: Human intestinal permeability is a key determinant of the oral fraction absorbed (f_a) of active pharmaceutical ingredients (APIs). This study evaluated the ability of an in-house canine Mdr1 (cMdr1) knockout (KO) Madin-Darby Canine Kidney (MDCK) cell line to correlate in vitro apparent permeability (P_app) with human small intestinal permeability (P_eff). In vitro P_app values of 16 reference compounds with high, medium, or low permeabilities were measured in the in-house cMdr1 KO MDCK protocol under pH gradient (6.5 ⇒ 7.4) and pH equivalent conditions (7.4 ⇒ 7.4) and correlations with human P_eff were established (R² > 0.8). The correlations were subsequently used to estim

SUBMITTER: Beran K 

PROVIDER: S-EPMC12505271 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature