title: Inhibitory effects of neuroleptics on debrisoquine oxidation in man.
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 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.
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D007546:Isoquinolines; D003647:Debrisoquin