Ciraulo D A, Alderson L M, Chapron D J, Jaffe J H, Subbarao B, Kramer P A
J Clin Psychopharmacol. 1982 Feb;2(1):2-7. doi: 10.1097/00004714-198202000-00002.
The disposition of orally administered imipramine (IMI) was studied in 11 depressed alcoholic and 12 depressed nonalcoholic male inpatients. Subjects received 50 mg three times daily for at least 10 days to ensure steady state. Following a temporary discontinuation of therapy, several blood samples were drawn over a 40-hour period. Imipramine, desipramine, and their 2-hydroxylated metabolites were measured in plasma using a high performance liquid chromatography assay. Eight hours following the last dose, alcoholics has significantly lower IMI (50 +/- 41 versus 106 +/- 46 ng/ml; p less than 0.005) and 2-hydroxyimipramine (12.8 +/- 7.5 versus 22.6 +/- 9.8 ng/ml; p less than 0.01) levels than controls. The mean terminal half-lives in the two groups were nearly identical (16.3 +/- 6.7 hours in alcoholics versus 17.1 +/- 5.4 hours in controls). Beck Depression Inventory scores were significantly reduced during IMI therapy (p less than 0.001) in the non-alcoholic controls, whereas no change was observed in the alcoholic group. These results are consistent with either a decrease in oral bioavailability of IMI in alcoholics or, assuming complete absorption, an increase in intrinsic clearance of 2.5 fold (2444 +/- 1151 versus 986 +/- 438 ml/min; p less than 0.005) over the clearance found in control subjects. The latter seems a more likely result of chronic ethanol intake. The fact that lower levels of IMI in the alcoholic group were accompanied by a lack of efficacy in relieving depressive symptomatology suggests that whether through an effect on bioavailability or intrinsic clearance, ethanol consumption is an important consideration when recommending tricyclic therapy.
对11名患有抑郁症的男性酗酒住院患者和12名患有抑郁症的男性非酗酒住院患者进行了口服丙咪嗪（IMI）处置情况的研究。受试者每日三次服用50毫克，持续至少10天以确保达到稳态。在治疗暂时中断后，在40小时内采集了几份血样。使用高效液相色谱分析法测定血浆中的丙咪嗪、去甲丙咪嗪及其2 - 羟基化代谢物。最后一剂药物服用8小时后，酗酒患者的丙咪嗪水平（50±41对106±46纳克/毫升；p＜0.005）和2 - 羟基丙咪嗪水平（12.8±7.5对22.6±9.8纳克/毫升；p＜0.01）显著低于对照组。两组的平均终末半衰期几乎相同（酗酒患者为16.3±6.7小时，对照组为17.1±5.4小时）。在非酗酒对照组中，丙咪嗪治疗期间贝克抑郁量表评分显著降低（p＜0.001），而酗酒组未观察到变化。这些结果与酗酒患者中丙咪嗪口服生物利用度降低一致，或者假设完全吸收，与对照受试者相比，内在清除率增加了2.5倍（2444±1151对986±438毫升/分钟；p＜0.005）。后者似乎更可能是长期乙醇摄入的结果。酗酒组中丙咪嗪水平较低且伴有缓解抑郁症状疗效不佳这一事实表明，无论通过对生物利用度还是内在清除率的影响，在推荐三环类药物治疗时，乙醇消耗都是一个重要的考虑因素。
