Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand.
J Clin Pharmacol. 2012 Mar;52(3):381-7. doi: 10.1177/0091270010396711. Epub 2011 Feb 22.
An increase in the area under the curve (AUC) after oral digoxin due to coadministration of drugs known as P-glycoprotein (P-gp) inhibitors has been reported in several studies, but there is very little information on the rate of absorption after P-gp inhibition. Based on an inverse Gaussian density absorption model and using a population approach, the authors reanalyzed data showing an increase in oral digoxin AUC in healthy volunteers after coadministration of talinolol. The model fitted the data well, and the results revealed that the maximum rate of digoxin absorption increased nearly 2-fold, whereas bioavailability increased only by 21%. It is concluded that the increase in the rate of absorption seems to be a better indicator of intestinal P-gp inhibition than the increase in extent of absorption. Furthermore, the authors use a simulation study to demonstrate the ability of the method to estimate bioavailability based on the population characteristics of digoxin disposition kinetics obtained from a different group of healthy volunteers.
已有多项研究报道，某些药物（称为 P-糖蛋白 [P-gp] 抑制剂）与地高辛同时给药后，地高辛的口服曲线下面积（AUC）增加，但关于 P-gp 抑制后吸收速率的信息却很少。基于逆高斯密度吸收模型并采用群体分析方法，作者重新分析了在健康志愿者中合用他林洛尔后地高辛 AUC 增加的数据。该模型拟合数据的效果良好，结果表明，地高辛吸收的最大速率几乎增加了 2 倍，而生物利用度仅增加了 21%。因此，作者得出结论，吸收速率的增加似乎比吸收程度的增加更能反映肠 P-gp 抑制。此外，作者还通过模拟研究证明了该方法能够基于从另一组健康志愿者中获得的地高辛处置动力学的群体特征来估计生物利用度。
