Hengstmann J H, Konen W, Konen C, Eichelbaum M, Dengler H J
Eur J Clin Pharmacol. 1975;8(1):33-9. doi: 10.1007/BF00616412.
The diminished sympathomimetic pressor activity of monohydroxylated phenylalkylamines after oral administration has been attributed to incomplete enteric absorption. Therefore, urinary excretion of the unchanged drug and its metabolites has been compared after intravenous and oral administration of 3H-m-octopamine to eight patients. Identical amounts of 3H-activity (80% of the dose) were excreted after the two routes of dosing, so enteric absorption has been assumed to be complete. Significant differences were found in the fraction of free urinary m-octopamine, which amounted to 10.5% of the dose after infusion and 0.58% after oral administration. The only metabolic pathways for m-octopamine are deamination and conjugation. Following oral administration the percentage of conjugates was considerably higher than after intravenous infusion. This metabolic pattern appears typical of all phenylalkylamines with a hydroxyl group in the meta position. Ring hydroxylation to catecholamines was not observed. The enzymes mainly responsible for conjugation after oral administration are located in the gut wall. The resulting ""first pass effect'', i.e. metabolism prior to the access to the central compartment, can account for the diminished pharmacodynamic effect after dosing by this route.
口服后单羟基化苯烷基胺类拟交感神经升压活性减弱被认为是由于肠道吸收不完全所致。因此，对8名患者静脉注射和口服3H -间羟胺后，比较了原形药物及其代谢产物的尿排泄情况。两种给药途径后排出的3H活性量相同（占剂量的80%），因此假定肠道吸收是完全的。发现游离尿间羟胺的比例存在显著差异，静脉输注后占剂量的10.5%，口服后占0.58%。间羟胺唯一的代谢途径是脱氨基和结合反应。口服给药后结合物的百分比明显高于静脉输注后。这种代谢模式似乎是所有间位带有羟基的苯烷基胺类的典型特征。未观察到环羟基化生成儿茶酚胺的情况。口服给药后主要负责结合反应的酶位于肠壁。由此产生的“首过效应”，即在进入中央室之前发生的代谢，可解释该给药途径给药后药效学效应减弱的原因。
