DEXTROMETHORPHAN PHENOTYPING AND HALOPERIDOL DISPOSITION IN SCHIZOPHRENIC-PATIENTS

This study examined the relationship between the metabolic ratios of d extromethorphan/dextrorphan, haloperidol disposition, and the incidenc e of extrapyramidal side effects in schizophrenic patients. Eighteen s chizophrenic patients were phenotyped with a test dose of dextromethor phan prior to the initiation of haloperidol treatment. The metabolic r atio of dextromethorphan/dextrorphan was determined in each patient. P atients were treated with oral haloperidol 10 mg/day for 2 weeks. Bloo d samples for haloperidol and reduced haloperidol were obtained at wee k 2 of haloperidol treatment. Haloperidol and reduced haloperidol plas ma concentrations were assayed by HPLC with electrochemical detection. Significant correlations of dextromethorphan/dextrorphan metabolic ra tios vs. plasma haloperidol concentrations, reduced haloperidol concen trations, and reduced haloperidol/haloperidol ratios were found (r = 0 .726, P = 0.0007; r = 0.782, P = 0.0001; and r = 0.619, P = 0.006, res pectively). Ten patients who experienced extrapyramidal side effects h ad higher reduced haloperidol concentrations and reduced haloperidol/h aloperidol ratios than the other patients (2.49 +/- 1.42 [S.D.] ng/ml vs. 1.10 +/- 0.46 ng/ml, P = 0.014 and 0.287 +/- 0.102 vs. 0.192 +/- 0 .065, P = 0.030). The former also had a trend to have higher haloperid ol concentrations and dextromethorphan/dextrorphan ratios than the lat ter (8.04 +/- 2.91 ng/nl vs. 5.83 +/- 1.79 ng/ml, P = 0.066 and 0.023 +/- 0.017 vs. 0.011 +/- 0.010, P = 0.077). Phenotyping patients has th e potential to assist clinicians in predicting plasma drug concentrati ons during the subsequent neuroleptic drug treatment. Further research with phenotyping and psychotropic drug metabolism in psychiatric pati ents is needed. (C) 1997 Elsevier Science Ireland Ltd.