Dujovne C A, Gustafson J H, Dickey R A
Clin Pharmacol Ther. 1982 Feb;31(2):187-94. doi: 10.1038/clpt.1982.30.
An experimental model was developed to allow extended investigation (up to3 days) of the kinetics of upper gastrointestinal elimination (including enterohepatic recirculation) of drugs or metabolites in normal subjects under near physiologic conditions. The test drug (100 mg carprofen) was given by mouth or through a triple-lumen nasogastric tube to the upper duodenum to three normal subjects. The amounts of drug and metabolite passing the gastrointestinal aspiration port for each time interval were calculated from the concentrations measured in the aspirate using dual nonabsorbable markers and continuous sampling and reinfusion of intestinal fluids. Crossover studies without intubation in the same subjects and comparisons to historical controls demonstrated that the intubation procedure did not affect normal kinetic data obtained from conventional blood and urine specimens. The model permits direct comparison of gastrointestinal-biliary clearance with renal and with total body clearance and is particularly useful in resolving kinetic questions of gastrointestinal-biliary excretion or recirculation of metabolites when a drug must be taken by mouth. Potential first-pass phenomena may also be investigated by means of incremental gastrointestinal clearance values.
建立了一个实验模型，以便在接近生理条件下，对正常受试者体内药物或代谢物的上消化道消除动力学（包括肠肝循环）进行长时间研究（长达3天）。将受试药物（100毫克卡洛芬）经口或通过三腔鼻胃管给予三名正常受试者的十二指肠上段。使用两种不可吸收标记物，并通过连续采样和回输肠液，根据吸出物中测得的浓度，计算每个时间间隔通过胃肠道抽吸端口的药物和代谢物量。在同一受试者中进行的无插管交叉研究以及与历史对照的比较表明，插管程序不影响从常规血液和尿液样本获得的正常动力学数据。该模型允许直接比较胃肠道-胆道清除率与肾清除率以及全身清除率，在解决药物必须口服时代谢物的胃肠道-胆道排泄或再循环的动力学问题方面特别有用。潜在的首过现象也可以通过增加的胃肠道清除率值进行研究。
