Tricyclic antidepressant and metabolite levels in chronic renal failure
Tricyclic antidepressant and metabolite levels in chronic renal failure
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慢性肾衰竭中的三环类抗抑郁药和代谢物水平
DOI：
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发表时间：
1985
期刊：
影响因子：
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通讯作者：
John M. Kane
中科院分区：
文献类型：
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作者：
J. Lieberman;T. Cooper;R. Suckow;Herbert Steinberg;M. Borenstein;R. Brenner;John M. Kane
从接受三环类抗抑郁药（TCAs）的12名接受血液透析的患者中抽取系列血液样本。在透析前、透析期间和透析后采集样本（每例受试者2 - 17次透析）。在β-葡萄糖醛酸酶/硫酸酯酶水解前后，通过HPLC分析样品，以测定结合和非结合代谢产物。对这些数据与抑郁症和正常肾功能的对照组数据进行比较的分析表明：（1）在稳态时，叔胺和仲胺TCA水平没有差异;（2）羟基化代谢物的水平具有更大的变异性，在稳态时略高;（3）结合羟基化化合物的水平显著升高，达到正常值的500%至1500%;（4）达到稳态水平的时间似乎略有增加;和（5）在我们的肾功能正常患者中，非结合和结合药物形式的消除半衰期比文献中报告的更长。三级、二级和羟基化代谢物的水平未因透析而改变，而葡萄糖醛酸化代谢物水平显著降低。这些结果表明结合药物形式的浓度增加，并表明非结合和结合代谢物的分布异常或消除延迟。这些观察结果可能揭示了这些患者对TCA副作用的明显超敏反应，特别是因为葡萄糖醛酸苷可能发挥外周药理学作用。
Serial blood samples were drawn from 12 patients undergoing hemodialysis who were receiving tricyclic antidepressants (TCAs). Samples were drawn before, during, and after a dialysis session (two to 17 sessions per subject). Samples were analyzed by HPLC before and after hydrolysis with β‐glucuronidase/sulfatase to determine the conjugated and nonconjugated metabolites. Analysis of these data in comparison with those of controls with depression and normal renal function showed that: (1) at steady state, tertiary and secondary amine TCA levels did not differ; (2) levels of the hydroxylated metabolites had greater variability and were somewhat higher at steady state; (3) levels of the conjugated hydroxylated compounds were markedly elevated, reaching 500% to 1500% normal; (4) the time to reach a steady‐state level appeared to be slightly increased; and (5) elimination t½s of unconjugated and conjugated drug forms were longer in our patients with normal renal function than those reported in the literature. Levels of the tertiary, secondary, and hydroxylated metabolites were not changed by dialysis, whereas there were substantial decrements in glucuronidated metabolite levels. These findings demonstrate increased concentrations of conjugated drug forms and suggest an abnormal distribution or delayed elimination of unconjugated and conjugated metabolites. These observations may shed some light on the apparent hypersensitivity of these patients to TCA side effects, particularly because glucuronides may exert peripheral pharmacologic effects.