Montgomery S A, McAuley R, Montgomery D B, Braithwaite R A, Dawling S
Clin Pharmacokinet. 1979 Mar-Apr;4(2):129-36. doi: 10.2165/00003088-197904020-00005.
20 routine patients with endogenous depression were investigated in a kinetic and 4 week treatment study. Steady-state plasma nortriptyline concentrations above 200 microgram/L were associated with a highly significant poorer therapeutic outcome. The correlations between the 24, 48 and 72 hour concentrations and steady-state concentration were very good (r = 0.81, 0.97, 0.94; p less than 0.0001) and better than the correlation between half-life and steady-state (r = 0.65; p less than 0.01). The Spearman rank correlations (Rs) between amelioration of depression measured by the Hamilton Rating Scale (HRS) and the 24, 48 and 72 hour concentrations were highly significant (Rs = 0.74, 0.79, 0.79; p less than 0.001) but for half-life (Rs = 0.33) the correlation was not significant. The single 48 hour plasma nortriptyline concentration following a single oral dose is recommended as a reliable simplified monitoring test suitable for a busy clinic. The test is useful for dosage adjustment to maximise antidepressant action and minimise toxicity. A tentative dosage adjustment schedule for individualising antidepressant treatment with nortriptyline based on the 48 hour or the 24 hour plasma concentration is proposed.
对20例内源性抑郁症患者进行了一项为期4周的动力学治疗研究。稳态血浆去甲替林浓度高于200微克/升与显著较差的治疗效果相关。24小时、48小时和72小时浓度与稳态浓度之间的相关性非常好(r = 0.81、0.97、0.94;p < 0.0001),优于半衰期与稳态之间的相关性(r = 0.65;p < 0.01)。用汉密尔顿评定量表(HRS)测量的抑郁改善与24小时、48小时和72小时浓度之间的斯皮尔曼等级相关性(Rs)非常显著(Rs = 0.74、0.79、0.79;p < 0.001),但与半衰期(Rs = 0.33)的相关性不显著。建议单次口服剂量后48小时的血浆去甲替林浓度作为一种可靠的简化监测试验,适用于繁忙的诊所。该试验有助于调整剂量,以最大限度地发挥抗抑郁作用并最小化毒性。提出了一种基于48小时或24小时血浆浓度个体化去甲替林抗抑郁治疗的初步剂量调整方案。