Wagner F, Jähnchen E, Trenk D, Eichelbaum M, Harnasch P, Hauf G, Roskamm H
Benedikt Kreutz Rehabilitationszentrum für Herz- und Kreislaufkranke, Bad Krozingen.
Klin Wochenschr. 1987 Dec 15;65(24):1164-8. doi: 10.1007/BF01733250.
A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.
一名47岁的冠心病患者因Ⅲ度房室传导阻滞、严重低血压和心室功能受损而休克，被收入冠心病监护病房。入院前一周开始使用标准剂量的美托洛尔（100毫克，每日三次，然后100毫克，每日两次）进行治疗。入院前两天，加用了地尔硫䓬（60毫克，每日两次）。血液样本分析显示，美托洛尔血浆浓度异常高（大于3000纳克/毫升），地尔硫䓬血浆浓度为526纳克/毫升。停用抗心绞痛治疗后1周内，患者康复。三个月后，让该患者单次服用美托洛尔、地尔硫䓬、普罗帕酮（因为他过去曾服用过这种药物）和司巴丁（作为氧化药物代谢中去甲丙咪嗪/司巴丁型多态性的探针）。发现他对这四种药物均为代谢缓慢者，表明它们的代谢受相同的基因控制。因此，在药物代谢中属于司巴丁/去甲丙咪嗪多态性代谢缓慢者表型的患者（占德国人口的6.4%），单独使用这些药物中的一种标准剂量进行治疗时，可能会出现药物不良反应。此外，预计在这一亚组患者中，同时使用这些常用药物尤其有害。
