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• W2152244549 abstract "First-pass effect has been an important concern for oral pharmaceuticals. An in vivo system was developed for measuring different concentrations of pharmaceuticals in the portal vein and hepatic vein (via the inferior vena cava) for delineating presystemic metabolism under different perfusion rates by using indinavir as an exemplary agent.An in situ single-pass intestinal perfusion technique was modified from previous studies to concomitantly obtain portal and hepatic venous bloods. Portal and hepatic venous samples were simultaneously taken from rats at appropriate time points using the perfusion model of 1 mg/mL indinavir at flow rates of 0.05, 0.1, 0.5 and 1.0 mL/min. The indinavir concentrations were assayed by binary-gradient high-pressure liquid chromatography with UV detection.The mean indinavir concentrations in portal vein concentration-time profiles at different perfusion times under various flow rates were all higher than those obtained for hepatic veins. At flow rates of 0.5 and 1.0 mL/min, in particular, the area under the curve (AUC) and maximal concentration (Cmax) of indinavir absorption were significantly different between portal veins and hepatic veins (p < 0.05), indicating considerable hepatic involvement in the presystemic extraction of indinavir. The system also has potential for use when estimating the hepatic extraction ratio (E(H)) and hepatic clearance (Cl(H)).This in vivo approach could provide another useful tool for improving our basic understanding of the absorption kinetics and hepatic metabolism of pharmaceuticals under development and facilitating the clinical application of such." @default.
• W2152244549 created "2016-06-24" @default.
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• W2152244549 date "2008-01-01" @default.
• W2152244549 modified "2023-10-05" @default.
• W2152244549 title "Application of Rat In Situ Single-pass Intestinal Perfusion in the Evaluation of Presystemic Extraction of Indinavir Under Different Perfusion Rates" @default.
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• W2152244549 doi "https://doi.org/10.1016/s0929-6646(08)60006-6" @default.
• W2152244549 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18218576" @default.
• W2152244549 hasPublicationYear "2008" @default.
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