title: Thiothixene pharmacokinetic interactions: a study of hepatic enzyme inducers, clearance inhibitors, and demographic variables.
abstract: Fifty-nine plasma thiothixene concentrations were measured in 42 patients as part of routine therapeutic drug monitoring. Data collection included concomitant medications, smoking history, and demographic variables. A retrospective analysis was performed to assess the effect of these parameters on oral thiothixene clearance. When groups of patients were categorized by concomitant medications (i.e., no interacting drugs, enzyme/clearance inducers, and enzyme/clearance inhibitors), thiothixene clearance was found to be significantly increased by enzyme inducing drugs (e.g., anticonvulsants) and decreased by clearance inhibiting agents (e.g., cimetidine). Tobacco smoking significantly increased the hepatic clearance of thiothixene within the no interactions and inhibitor groups, but not in the inducer group. Significantly more patients in the inducer group had nondetectable plasma concentrations of thiothixene than the other groups. When the entire patient population was dichotomized by age, patients less than 50 years old had a significantly greater mean clearance (48.2 +/- 37.8 liters/min) versus those greater than or equal to 50 (20.0 +/- 12.6 liters/min). Men in this cohort exhibited a significantly higher clearance (49.2 +/- 38.7 liters/min) than did the women (22.0 +/- 13.5 liters/min). By taking into account these potential sources of pharmacokinetic variability when monitoring plasma thiothixene concentrations, more appropriate dosing of thiothixene may be achieved. Controlled, prospective studies are needed to validate these findings.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7765.
authors.forename: L
authors.initials: L
authors.lastname: Ereshefsky
authors.forename: S R
authors.initials: SR
authors.lastname: Saklad
authors.forename: M D
authors.initials: MD
authors.lastname: Watanabe
authors.forename: C M
authors.initials: CM
authors.lastname: Davis
authors.forename: M W
authors.initials: MW
authors.lastname: Jann
mesh_terms: D000284:Administration, Oral; D000328:Adult; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000188:drug therapy / Q000201:enzymology* / Q000523:psychology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy / Q000201:enzymology* / Q000523:psychology; D012189:Retrospective Studies; D013888:Thiothixene / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D013888:Thiothixene