ACT178882是一种新的Renin抑制剂,其IC50值为1.4nM.
ACT 178882 is a new Renin inhibitor with an IC50 of 1.4 nM.
The median time to Cmax (tmax) for ACT 178882 is prolonged from 3.5 to 5.0 h by diltiazem whereas its apparent terminal half-life (t?) is unaffected by diltiazem, 22.9 and 24.2 h for treatments A and B, respectively. Using treatment A as reference, the geometric mean ratio (90% CI) is 1.62 (1.36 to 1.94) for Cmax and 2.02 (1.75 to 2.34) for AUC∞, indicating a significant interaction between ACT 178882 and diltiazem[2].
[1]. Corminboeuf O, et al. Piperidine-based renin inhibitors: upper chain optimization. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6291-6. [2]. Dingemanse J, et al. Drug-drug interaction study of ACT-178882, a new renin inhibitor, and diltiazem in healthy subjects. Clin Drug Investig. 2013 Mar;33(3):207-13.
Cell experiment: | Venous blood samples for the determination of ACT 178882 are drawn at the following time points: pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96 and 120 h after dosing with ACT 178882 in treatment A and pre-dose and 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216 and 240 h after dosing with ACT178882 in treatment B. For diltiazem as soon as possible after collection, and for ACT-178882 within maximally 30 minutes after collection, the tubes are centrifuged and the plasma separated. All samples are stored in an upright position at -20 °C (ACT 178882) or -80 °C (diltiazem) or below pending analysis[2]. |
参考文献: [1]. Corminboeuf O, et al. Piperidine-based renin inhibitors: upper chain optimization. Bioorg Med Chem Lett. 2010 Nov 1;20(21):6291-6. | |
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