Intestinal absorption barriers and transport mechanisms, including secretory transport, for a cyclic peptide, fibrinogen antagonist.
作者： Bruce J. Aungst , Hiroshi Saitoh
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摘要: Purpose. The intestinal absorption of DMP 728, a cyclic peptide fibrinogen antagonist, was examined with the goals identifying cause(s) its low oral bioavailability and understanding mechanisms transport. Methods. In vitro partitioning, metabolism, permeation through rat segments were evaluated. Results. 728 had lipophilicity rates relative to model compounds. addition, in secretory direction greatly exceeded transport absorptive direction. saturable, glucose-dependent, inhibited by verapamil monoclonal antibody P-glycoprotein. likewise verapamil. Mucosal-to-serosal increased going from proximal distal sites, but lower than serosal-to-mucosal for each site. Conclusions. Net are major barriers 728.
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