Thioridazine interferences with imipramine metabolism and measurement.
A case is presented in which toxic concentrations of imipramine (Tofranil) resulted from the co-administration of low-dose thioridazine (Mellaril). This probably occurred in an individual with genetically reduced capacity for oxidative drug metabolism, specifically via thioridazine's interference with the hepatic cytochrome P450IID6 isoenzyme (CYP2D6). In addition, coelution of thioridazine and its metabolites resulted in false elevations of imipramine and desipramine as measured by a common high-performance liquid chromatography (HPLC) method (cyanopropyl column). In contrast, an enzyme immunoassay (Abbott TDxFLx) and a second reference HPLC method (silica column) accurately resolved the analytes. This combination of psychiatric drugs is not uncommon in the pediatric population and is one of which both clinicians and laboratorians need to be aware. To the author's knowledge, this is the first report of interferences of thioridazine with both the metabolism and measurement of imipramine in a pediatric patient.
Maynard
G L
GL
Laboratory Corporation of America, University of Utah School of Medicine, Salt Lake City, USA.
Soni
P
P
D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000097:blood; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D002648:Child; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008297:Male; D013881:Thioridazine / Q000008:administration & dosage* / Q000097:blood
D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D013881:Thioridazine; D007099:Imipramine