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• W2040544202 abstract "Peptidic drugs such as β-lactam aminocephalosporin antibiotics (e.g., cephalexin) and the ACE inhibitors lisinopril, quinapril, and benzazepril are apparently absorbed, at least in part, by the intestinal dipeptide transporter system (DTS). Although many properties of the DTS have been elucidated, including isolation of the carrier protein, little is known about the distribution of this transporter along the gastrointestinal (GI) tract. The objectives of the present study were to (1) validate that SQ-29852 (a lysylproline ACE inhibitor) is a stable and specific probe for evaluation of the DTS in rats and (2) provide fundamental in vivo information on the distribution of the DTS along the GI tract of rats. Most of the previous studies that explored the location of the DTS typically involved either in vitro uptake or in situ disappearance of unstable or nonspecific probes. SQ-29852, on the other hand, is an ideal probe for evaluation of the DTS because it is chemically and metabolically stable and it is absorbed almost exclusively by the DTS. SQ-29852 appears to be a specific probe for the DTS because the dose-dependent reduction in absorption from about 60% to less than 8% (3 and 3000 mg/kg, respectively) suggests that at least 85% of an orally administered low dose of SQ-29852 is absorbed by a saturable process, which was shown previously to be the DTS. [14C]SQ-29852 was administered by gavage to intact rats and via an indwelling cannula in one of the following sections of the intestine: duodenum, jejunum, ileum and proximal colon (n= 4 for each site). On the basis of the recovery of [14C]SQ-29852 in urine, the DTS is apparently distributed throughout the entire GI tract of rats, including the proximal colon. The present results are consistent with previously reported results on the absorption of natural dipeptides in humans and rats and immunohistochemical evaluation in rats; however, they disagree with a recent report in humans with amoxicillin. This difference is discussed in terms of the specificity and stability of various drugs that have been used as probes of the DTS." @default.
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• W2040544202 date "1996-03-01" @default.
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• W2040544202 title "Distribution of the Dipeptide Transporter System along the Gastrointestinal Tract of Rats Based on Absorption of a Stable and Specific Probe, SQ-29852" @default.
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• W2040544202 doi "https://doi.org/10.1021/js950017t" @default.
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