Lund J, Christensen J A, Bechgaard E, Molander L, Larsson H
Acta Pharmacol Toxicol (Copenh). 1979 Mar;44(3):177-84. doi: 10.1111/j.1600-0773.1979.tb02314.x.
The pharmacokinetics of a structurally new 5HT-uptake inhibitor, femoxetine (FG 4963), with antidepressant properties have been investigated in man using a radioactive as well as a non-labelled substance. A two compartment open model gives a good description of the data, both after oral and intravenous administration. The substance was almost completely absorbed after an oral dose, but only 5-10% reached the systemic circulation due to extensive first pass metabolism. The metabolites had distribution and excretion rates similar to the parent compound. Only a small part (less than 2%) was excreted as femoxetine in the urine. The urinary excretion of the parent compound varied more than a 100-fold depending on the pH of the urine. The urine pH, however, did not influence the plasma concentration of femoxetine. Most of the substance (up to 80%) was eliminated by urinary excretion of metabolites, and only a small part of the radioactive dose was excreted in the faeces (up to 11%). The pharmacokinetic parameters were not found to be dose dependent in the range investigated, but it was not possible to decide whether the bioavailability was dependent on the dose. The variation between subjects was rather large, giving only a limited possibility for prediction of the plasma concentration from one subject to another.
一种具有抗抑郁特性的结构新型5-羟色胺摄取抑制剂非莫西汀（FG 4963）的药代动力学已在人体中使用放射性物质和非标记物质进行了研究。双室开放模型能很好地描述口服和静脉给药后的实验数据。口服给药后，该物质几乎完全被吸收，但由于广泛的首过代谢，只有5-10%的药物进入体循环。代谢产物的分布和排泄速率与母体化合物相似。只有一小部分（不到2%）以非莫西汀的形式经尿液排泄。母体化合物的尿排泄量因尿液pH值不同而相差100多倍。然而，尿液pH值并不影响非莫西汀的血浆浓度。大部分药物（高达80%）通过代谢产物经尿液排泄消除，只有一小部分放射性剂量经粪便排泄（高达11%）。在所研究的剂量范围内，未发现药代动力学参数与剂量相关，但无法确定生物利用度是否依赖于剂量。个体之间的差异相当大，因此从一个个体预测另一个个体的血浆浓度的可能性有限。
