Daniel W, Adamus A, Melzacka M, Szymura J, Vetulani J
Naunyn Schmiedebergs Arch Pharmacol. 1981 Nov;317(3):209-13. doi: 10.1007/BF00503818.
Pharmacokinetics of imipramine (IMI) and its active metabolite, desipramine (DMI) was studied in rats after administration of a single dose of 10 mg/kg IMI, or after chronic administration of this dose once or twice a day for 14 days. The elimination curves of IMI and DMI from the blood and brain show that both the whole body and the brain behave as multi-compartment systems. Maximum concentrations of IMI and DMI in blood and brain appear at the same time, indicating rapid metabolism of IMI: the concentrations were significantly higher in the brain than in the blood. After the chronic treatment the maximum blood and cerebral levels of IMI and DMI were not much higher than after a single dose, but the elimination was slowed down. Brain concentration of IMI and DMI and brain IMI/DMI concentration ratio do not parallel those in the blood. After a prolonged treatment, once or twice a day, desipramine in the brain is present for the whole period between injections at concentrations sufficient to inhibit the noradrenaline uptake. If the drug is given twice a day, in addition to DMI also IMI is present for the whole time at concentration which may inhibit also serotonin uptake.
在大鼠单次给予10mg/kg丙咪嗪（IMI）后，或每天一次或两次连续14天给予该剂量进行慢性给药后，研究了丙咪嗪（IMI）及其活性代谢产物地昔帕明（DMI）的药代动力学。IMI和DMI从血液和大脑中的消除曲线表明，全身和大脑均表现为多室系统。IMI和DMI在血液和大脑中的最大浓度同时出现，表明IMI代谢迅速：大脑中的浓度显著高于血液中的浓度。慢性治疗后，IMI和DMI的最大血液和脑水平并不比单次给药后高多少，但消除速度减慢。大脑中IMI和DMI的浓度以及大脑中IMI/DMI浓度比与血液中的情况不平行。在每天一次或两次的长期治疗后，大脑中的地昔帕明在两次注射之间的整个时间段内都以足以抑制去甲肾上腺素摄取的浓度存在。如果每天给药两次，除了DMI外，IMI在整个时间段内也以可能抑制5-羟色胺摄取的浓度存在。
