多次给药后的复杂吸收分析：在 P-糖蛋白底物他林洛尔和利福平相互作用中的应用。
Analysis of Complex Absorption After Multiple Dosing: Application to the Interaction Between the P-glycoprotein Substrate Talinolol and Rifampicin.
机构信息
Department of Pharmacology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
出版信息
Pharm Res. 2022 Dec;39(12):3293-3300. doi: 10.1007/s11095-022-03397-6. Epub 2022 Sep 26.
PURPOSE
In order to clarify the effect of rifampicin on the bioavailability of the P-glycoprotein substrate talinolol, its absorption kinetics was modeled after multiple-dose oral administration of talinolol in healthy subjects.
METHODS
A sum of two inverse Gaussian functions was used to calculate the time course of the input rate into the systemic circulation.
RESULTS
The estimated rate of drug entry into the systemic circulation revealed two distinct peaks at 1 and 3.5 h after administration. Rifampicin did not affect bioavailability of talinolol, but did shift the second peak of the input function by 1.3 h to later times. Elimination clearance and one of the intercompartmental distribution clearances increased significantly under rifampicin treatment.
CONCLUSIONS
Rifampicin changes the time course of absorption rate but not the fraction absorbed of talinolol. The model suggests the existence of two intestinal absorption windows for talinolol.
目的
为了阐明利福平对 P-糖蛋白底物他林洛尔生物利用度的影响，在健康受试者中单剂量口服他林洛尔后，对其吸收动力学进行了模型研究。
方法
采用两个逆高斯函数的总和来计算药物进入体循环的时间过程。
结果
估计的药物进入体循环的速度在给药后 1 和 3.5 小时出现两个明显的峰值。利福平不影响他林洛尔的生物利用度，但将输入函数的第二个峰值转移到 1.3 小时后。利福平治疗后，消除清除率和一个隔室间分布清除率显著增加。
结论
利福平改变了他林洛尔的吸收速率时间过程，但不改变其吸收分数。该模型表明他林洛尔存在两个肠吸收窗。
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