Syvälahti E K, Lindberg R, Kallio J, De Vocht M
Br J Clin Pharmacol. 1986 Jul;22(1):89-92.
Liver oxidative metabolism, assessed by debrisoquine hydroxylation test, was studied in 107 healthy volunteers and in 71 patients with or without neuroleptic drug treatment. The mean metabolic ratio (MR = debrisoquine/4-hydroxydebrisoquine excretion in the urine) was 2.8 +/- 0.1 (s.e. mean) in the control group, six persons being poor metabolizers of debrisoquine (MR greater than or equal to 12.6). The mean MR (12.1 +/- 1.5) was significantly higher in those 42 patients taking neuroleptics than in patients without neuroleptics (0.8 +/- 0.1). In the former group, seventeen patients had a MR exceeding 12.6. Oral contraceptives, antiepileptics, benzodiazepines and progestin derivates did not increase MR values, the highest individual ratio being 2.72 in those subjects not receiving neuroleptics. These results suggest a probable competitive inhibition of oxidative metabolism by neuroleptics. This is a phenomenon of potential clinical importance both in patients with an inherited poor metabolic capacity and in patients receiving other drugs like beta-adrenoceptor blocking agents and tricyclic antidepressants oxidized by the same enzyme system.
通过异喹胍羟基化试验评估肝脏氧化代谢，对107名健康志愿者以及71名接受或未接受抗精神病药物治疗的患者进行了研究。对照组的平均代谢率（MR = 异喹胍/尿中4 - 羟基异喹胍排泄量）为2.8±0.1（标准误均值），6人是异喹胍的代谢不良者（MR≥12.6）。服用抗精神病药物的42名患者的平均MR（12.1±1.5）显著高于未服用抗精神病药物的患者（0.8±0.1）。在前一组中，17名患者的MR超过12.6。口服避孕药、抗癫痫药、苯二氮䓬类药物和孕激素衍生物并未增加MR值，未接受抗精神病药物治疗的受试者中个体最高比值为2.72。这些结果表明抗精神病药物可能对氧化代谢有竞争性抑制作用。这一现象在遗传性代谢能力差的患者以及接受其他由同一酶系统氧化的药物（如β - 肾上腺素受体阻滞剂和三环类抗抑郁药）治疗的患者中具有潜在的临床重要性。
