Mellström B, Bertilsson L, Träskman L, Rollins D, Asberg M, Sjöqvist F
Pharmacology. 1979;19(5):282-7. doi: 10.1159/000137324.
The two structurally similar tricyclic antidepressant drugs amitriptyline (AT) and chlorimipramine (CI) were administered to 15 patients in a cross-over study. Approximately equimolar daily doses of the two drugs (5 mumol/kg body weight) were given as commercial tablets. Steady state plasma levels of the parent drugs and the demethyl metabolites were determined by high performance liquid chromatography. An about 5-fold interindividual variation was found in plasma levels of all four compounds. As the reciprocal plasma level during multiple dosing is proportional to the clearance of a compound, this parameter was used for linear regression analysis. In the 15 patients there was a significant correlation between the reciprocal plasma levels of CI and its metabolite demethylchlorimipramine (r = 0.76; p less than 0.001) and also between AT and its metabolite nortriptyline (r = 0.52; p less than 0.05). The reciprocal plasma levels of the parent compounds AT and CI were closely correlated (r = 0.87; p less than 0.001). A similar correlation was found for the demethyl metabolites (r = 0.77; p less than 0.001). The results indicate that similar factors control the plasma levels of AT and CI during treatment and that similar enzymes may be involved in the metabolism of the two drugs.
在一项交叉研究中，给15名患者服用了两种结构相似的三环类抗抑郁药阿米替林（AT）和氯米帕明（CI）。以市售片剂形式给予两种药物大约等摩尔的每日剂量（5 μmol/kg体重）。通过高效液相色谱法测定母体药物及其去甲基代谢物的稳态血浆水平。发现所有四种化合物的血浆水平存在约5倍的个体间差异。由于多次给药期间的倒数血浆水平与化合物的清除率成正比，该参数用于线性回归分析。在这15名患者中，CI与其代谢物去甲氯米帕明的倒数血浆水平之间存在显著相关性（r = 0.76；p < 0.001），AT与其代谢物去甲替林之间也存在显著相关性（r = 0.52；p < 0.05）。母体化合物AT和CI的倒数血浆水平密切相关（r = 0.87；p < 0.001）。去甲基代谢物也发现了类似的相关性（r = 0.77；p < 0.001）。结果表明，在治疗期间，类似的因素控制着AT和CI的血浆水平，并且两种药物的代谢可能涉及类似的酶。
