pkquest measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokineticspkquest测量肠道吸收和第一遍新陈代谢u2014u2014应用人类酒精药物动力学.pdfVIP

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pkquest measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokineticspkquest测量肠道吸收和第一遍新陈代谢u2014u2014应用人类酒精药物动力学.pdf

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pkquest measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokineticspkquest测量肠道吸收和第一遍新陈代谢u2014u2014应用人类酒精药物动力学

BMC Clinical Pharmacology BioMed Central BMC Clinical Pharmacology x 2002, 2 Research article PKQuest: measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokinetics David G Levitt Address: Department of Physiology 6-125 Jackson Hall 321 Church St. S. E. Minneapolis, MN 55455, USA E-mail: levitt@ Published: 15 August 2002 Received: 4 April 2002 Accepted: 15 August 2002 BMC Clinical Pharmacology 2002, 2:4 This article is available from: /1472-6904/2/4 © 2002 Levitt; licensee BioMed Central Ltd. This article is published in Open Access: verbatim copying and redistribution of this article are permitted in all media for any non-commercial purpose, provided this notice is preserved along with the articles original URL. Abstract Background: PKQuest, a new physiologically based pharmacokinetic (PBPK) program, is applied to human ethanol data. The classical definition of first pass metabolism (FPM) based on the differences in the area under the curve (AUC) for identical intravenous and oral doses is invalid if the metabolism is non-linear (e.g. ethanol). Uncertainties in the measurement of FPM have led to controversy about the magnitude of gastric alcohol metabolism. PKQuest implements a new, rigorous definition of FPM based on finding the equivalent intravenous input function that would produce a blood time course identical to that observed for the oral intake. This input function equals the peripheral availability (PA) and the