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• W2002685428 abstract "BIO1211 is a small peptidyl potent antagonist of the activated form of alpha4beta1 integrin. The effect of enalapril on the in vitro and in vivo cleavage of BIO1211 was investigated. In heparinized blood, plasma and rat liver, lung and intestinal homogenates, BIO1211 was converted rapidly to BIO1588 by hydrolytic cleavage of the terminal dipeptide moiety. This cleavage could be inhibited by EDTA and the ACE inhibitor, enalaprilat, the de-esterified acid derivative of enalapril. Enalaprilat inhibited the hydrolysis of BIO1211 in a concentration-dependent manner with IC(50) values of 2 nM in human and sheep plasma and 10 nM in rat plasma. In rat lung homogenate supernatant, the maximum inhibition of the conversion of BIO1211 to BIO1588 was approximately 80% at 1 microM with no further effect up to 100 microM of enalaprilat. Following a concomitant IV administration of enalapril and BIO1211 at 3 mg/kg each, the AUC and the half-life values of BIO1211 increased 18- and 10-fold, respectively. The AUC of BIO1588 decreased approximately 2-fold with no change in its plasma half-life. When rats were dosed intravenously with enalapril followed by an intratracheal dose of BIO1211, there was approximately 2.5-fold decrease in the AUC of BIO1588 and a 2.4-fold increase in its plasma half-life." @default.
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• W2002685428 date "2007-05-01" @default.
• W2002685428 modified "2023-09-26" @default.
• W2002685428 title "Effect of enalapril on the<b><i>in vitro</i></b>and<b><i>in vivo</i></b>peptidyl cleavage of a potent VLA-4 antagonist" @default.
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• W2002685428 doi "https://doi.org/10.1080/00498250701316663" @default.
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