Montgomery S A, Baldwin D, Shah A, Green M, Fineberg N, Montgomery D
Academic Department of Psychiatry, Medical School, St. Mary's Hospital, London, England.
Clin Neuropharmacol. 1990;13 Suppl 1:S71-5. doi: 10.1097/00002826-199001001-00008.
The results of pharmacokinetic studies of two recent 5-HT uptake inhibitors, zimelidine and fluoxetine, have pointed to the inadequacy of open-dose rising studies for establishing the most appropriate dose of new antidepressants. High plasma concentrations of the active metabolites, norzimelidine and norfluoxetine, were associated with a poorer therapeutic response in patients suffering from major depression. High drug plasma concentrations are also associated with increased side effects. Large fixed-dose placebo controlled studies with fluoxetine have confirmed the findings of the small pharmacokinetic study that lower doses are more effective. Fixed-dose pharmacokinetic studies are recommended as part of the program to establish the best dose of new antidepressants.
最近对两种5-羟色胺摄取抑制剂齐美利定和氟西汀的药代动力学研究结果表明，开放剂量递增研究不足以确定新型抗抑郁药的最合适剂量。活性代谢产物去甲齐美利定和去甲氟西汀的高血浆浓度与重度抑郁症患者较差的治疗反应相关。高药物血浆浓度还与副作用增加有关。氟西汀的大样本固定剂量安慰剂对照研究证实了小型药代动力学研究的结果，即较低剂量更有效。建议进行固定剂量药代动力学研究，作为确定新型抗抑郁药最佳剂量方案的一部分。
