Rollins D E, Alván G, Bertilsson L, Gillette J R, Mellström B, Sjöqvist F, Träskman L
Clin Pharmacol Ther. 1980 Jul;28(1):121-9. doi: 10.1038/clpt.1980.140.
Amitriptyline (AT) and its demethyl metabolite nortriptyline (NT) were given orally and intramuscularly to 6 normal subjects, and the areas under the blood concentration--time curves (AUC) were calculated. The mean unbound fraction of AT and NT in plasma was 5.4% and 8.3%, respectively. The blood-plasma ratio of NT was nearly double that of AT, which was close to unity. The mean systemic availability of oral relative to intramuscular AT and NT was 43% and 61%. The calculated mean oral blood clearance of AT as measured by dose (oral)/AUC was 1.6 1/min. The demethylation of orally administered AT varied considerably between the 6 individuals (from 25% to 89%) and correlated with oral drug clearance. Demethylation was estimated from the AUC applied to the NT metabolite. The estimated oral clearance of AT from demethylation ranged from 0.21 to 1.80 1/min.
对6名正常受试者口服和肌肉注射阿米替林（AT）及其去甲基代谢产物去甲替林（NT），并计算血药浓度-时间曲线下面积（AUC）。血浆中AT和NT的平均游离分数分别为5.4%和8.3%。NT的血-浆比几乎是AT的两倍，AT的血-浆比接近1。口服AT和NT相对于肌肉注射的平均全身生物利用度分别为43%和61%。通过剂量（口服）/AUC计算得出的AT平均口服血清除率为1.6升/分钟。口服AT的去甲基化在6名个体之间差异很大（从25%到89%），且与口服药物清除率相关。去甲基化是根据应用于NT代谢产物的AUC估算的。通过去甲基化估算的AT口服清除率范围为0.21至1.80升/分钟。
