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核心技术专利：CN118964589B侵权必究

核心技术专利：CN118964589B侵权必究

Dickinson R G, King A R, McKinnon G E, Hooper W D, Eadie M J, Herkes G K

Department of Medicine, University of Queensland, Brisbane, Australia.

Br J Clin Pharmacol. 1993 Jun;35(6):609-13. doi: 10.1111/j.1365-2125.1993.tb04190.x.

In five healthy male volunteers given multiple doses of diflunisal (DF), renal clearances (CLR) of the acyl glucuronide (DAG), phenolic glucuronide (DPG) and sulphate (DS) conjugates were about 42, 25 and 13 ml min-1, respectively. 2. These relatively low CLR values are probably due largely to the very high plasma protein binding of the conjugates, found in vitro to be 99.0%, 97.8% and 99.45%, respectively. 3. Thus glomerular filtration plays the minor and active tubular secretion the major role in renal excretion of the three conjugates. 4. This conclusion was supported by the effect of probenecid co-administration, which decreased CLR of DAG and DPG by about 70%. CLR for DS could not be calculated when probenecid was co-administered (because of interference by probenecid metabolites in the analysis of DS in urine). 5. Water-induced diuresis had no effect on CLR of the DF conjugates, consistent with tubular reabsorption being negligible.

在五名多次服用双氟尼酸（DF）的健康男性志愿者中，酰基葡萄糖醛酸（DAG）、酚类葡萄糖醛酸（DPG）和硫酸盐（DS）结合物的肾清除率（CLR）分别约为42、25和13 ml/min。2. 这些相对较低的CLR值可能主要归因于结合物与血浆蛋白的高度结合，体外实验发现其结合率分别为99.0%、97.8%和99.45%。3. 因此，肾小球滤过在这三种结合物的肾排泄中起次要作用，而肾小管主动分泌起主要作用。4. 丙磺舒共同给药的效果支持了这一结论，丙磺舒使DAG和DPG的CLR降低了约70%。当丙磺舒共同给药时，无法计算DS的CLR（因为丙磺舒代谢物干扰了尿液中DS的分析）。5. 水诱导利尿对DF结合物的CLR没有影响，这与肾小管重吸收可忽略不计一致。

Dickinson R G, King A R, McKinnon G E, Hooper W D, Eadie M J, Herkes G K

Department of Medicine, University of Queensland, Brisbane, Australia.

Br J Clin Pharmacol. 1993 Jun;35(6):609-13. doi: 10.1111/j.1365-2125.1993.tb04190.x.

In five healthy male volunteers given multiple doses of diflunisal (DF), renal clearances (CLR) of the acyl glucuronide (DAG), phenolic glucuronide (DPG) and sulphate (DS) conjugates were about 42, 25 and 13 ml min-1, respectively. 2. These relatively low CLR values are probably due largely to the very high plasma protein binding of the conjugates, found in vitro to be 99.0%, 97.8% and 99.45%, respectively. 3. Thus glomerular filtration plays the minor and active tubular secretion the major role in renal excretion of the three conjugates. 4. This conclusion was supported by the effect of probenecid co-administration, which decreased CLR of DAG and DPG by about 70%. CLR for DS could not be calculated when probenecid was co-administered (because of interference by probenecid metabolites in the analysis of DS in urine). 5. Water-induced diuresis had no effect on CLR of the DF conjugates, consistent with tubular reabsorption being negligible.

在五名多次服用双氟尼酸（DF）的健康男性志愿者中，酰基葡萄糖醛酸（DAG）、酚类葡萄糖醛酸（DPG）和硫酸盐（DS）结合物的肾清除率（CLR）分别约为42、25和13 ml/min。2. 这些相对较低的CLR值可能主要归因于结合物与血浆蛋白的高度结合，体外实验发现其结合率分别为99.0%、97.8%和99.45%。3. 因此，肾小球滤过在这三种结合物的肾排泄中起次要作用，而肾小管主动分泌起主要作用。4. 丙磺舒共同给药的效果支持了这一结论，丙磺舒使DAG和DPG的CLR降低了约70%。当丙磺舒共同给药时，无法计算DS的CLR（因为丙磺舒代谢物干扰了尿液中DS的分析）。5. 水诱导利尿对DF结合物的CLR没有影响，这与肾小管重吸收可忽略不计一致。