el-Yazigi A, Chaleby K, Gad A, Raines D A
Biological and Medical Research Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, Kingdom of Saudi Arabia.
J Clin Pharmacol. 1995 Jan;35(1):17-21. doi: 10.1002/j.1552-4604.1995.tb04740.x.
The steady-state kinetics of amitriptyline (AMI), fluoxetine (FLU), and their active metabolites nortriptyline (NTRIP) and norfluoxetine (NFLU) were studied in 15 patients treated once daily for long durations with 50 mg of AMI and 20 mg of FLU. These compounds were analyzed simultaneously in plasma by liquid chromatography. The means and (SEM) of the steady-state concentrations (Css) of AMI, NTRIP, FLU, and NFLU were 80.6 (14.2), 52.6 (10.3), 85.3 (16.1), and 90 (13.6) ng/mL, respectively, and the apparent oral clearances (CLor) of AMI and FLU were 42.4 (8.6) and 14.9 (2.5) L/hr, respectively. The metabolite/drug steady-state concentration ratio (Css(m)/Css) for NTRIP/AMI was 0.75 (0.14) and for NFLU/FLU was 1.27 (0.17). There was a significant correlation (P < 0.05) between Css of FLU and that of AMI or NTRIP. The Css and Css(m)/Css values obtained for AMI were higher (P < 0.056 and P < 0.0034, respectively) than those we observed in 10 patients treated solely with the same dose of AMI. The twofold increase in Css of AMI and ninefold increase in Css of NTRIP seem to be the result of inhibition of the metabolism of these compounds by FLU, particularly the ring hydroxylation. Norfluoxetine may have a small inhibitory influence on the metabolism of NTRIP but lacks this effect on the metabolism of AMI.
对15名长期每日服用50毫克阿米替林（AMI）和20毫克氟西汀（FLU）的患者，研究了阿米替林、氟西汀及其活性代谢产物去甲替林（NTRIP）和去甲氟西汀（NFLU）的稳态动力学。通过液相色谱法同时分析血浆中的这些化合物。AMI、NTRIP、FLU和NFLU的稳态浓度（Css）均值及标准误（SEM）分别为80.6（14.2）、52.6（10.3）、85.3（16.1）和90（13.6）纳克/毫升，AMI和FLU的表观口服清除率（CLor）分别为42.4（8.6）和14.9（2.5）升/小时。NTRIP/AMI的代谢产物/药物稳态浓度比（Css(m)/Css）为0.75（0.14），NFLU/FLU的该比值为1.27（0.17）。FLU的Css与AMI或NTRIP的Css之间存在显著相关性（P<0.05）。AMI的Css及Css(m)/Css值高于（分别为P<0.056和P<0.0034）我们在仅接受相同剂量AMI治疗的10名患者中观察到的值。AMI的Css增加两倍和NTRIP的Css增加九倍似乎是FLU抑制这些化合物代谢的结果，尤其是环羟基化。去甲氟西汀可能对NTRIP的代谢有轻微抑制作用，但对AMI的代谢没有这种作用。
