INHIBITORY EFFECTS OF NEUROLEPTICS ON DEBRISOQUINE OXIDATION IN MAN

  • 1 July 1986
    • journal article
    • research article
    • Vol. 22  (1) , 89-92
Abstract
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 in debrisoquine (MR .gtoreq. 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 derivatives 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.