Alván G, Borga O, Lind M, Palmér L, Siwers B
Eur J Clin Pharmacol. 1977 Mar 11;11(3):219-24. doi: 10.1007/BF00606414.
Nortriptyline was given orally and intramuscularly to six depressed patients. Plasma concentrations of parent drug and the unconjugated and conjugated principal metabolite, 10-hydroxynortriptyline, were determined by mass fragmentography. There was a significant decrease in the area under the nortriptyling plasma concentration- time curve after the oral route of administration, whilst the elimination rate was unchanged. With the oral dose, plasma concentrations of the metabolites were higher and peaked earlier than after intramuscular administration, whilst the opposite was true for the parent compound. This proves that the difference in bioavailability between the two routes of administration was due to first pass metabolism. As determined from the ratio between corresponding areas, the relative bioavailability of the oral dose was 66 +-21 S.D. per cent. This fraction is higher than that reported previously when intravenous nortriptyline was used as the reference dosage form.
对6名抑郁症患者口服和肌肉注射去甲替林。通过质量碎片分析法测定母体药物以及未结合和结合的主要代谢物10-羟基去甲替林的血浆浓度。口服给药后，去甲替林血浆浓度-时间曲线下面积显著降低，而消除率不变。口服给药时，代谢物的血浆浓度高于肌肉注射后，且峰值出现得更早，而母体化合物的情况则相反。这证明两种给药途径生物利用度的差异是由于首过代谢。根据相应面积的比值确定，口服剂量的相对生物利用度为66±21标准差百分比。该分数高于先前以静脉注射去甲替林作为参考剂型时报道的分数。
