title: Combined therapy with thioridazine decreases plasma levels of quetiapine inTaiwanese schizophrenic patients.
abstract: BACKGROUND
  In this study, the authors studied the effect of thioridazine (TDZ) on the pharmacokinetic profile of quetiapine (QTP) in Taiwanese patients with schizophrenia.
  
  
  METHODS
  Sixteen subjects with schizophrenia were recruited for this study. The authors pretreated 8 patients with TDZ 50 mg daily continuously given until the end of the study. QTP was administered to all the participants, and their doses were escalated to 300 mg once daily over a 7-day period and maintained for another week. On day 15, blood samples were collected at 12 time points within an 8-hour interval. The authors assayed the plasma levels of QTP with a high-performance liquid chromatography system coupled with ultraviolet detector.
  
  
  RESULTS
  Significantly decreased plasma levels of QTP after oral administration were observed in patients comedicated with TDZ compared with the QTP monotherapy group at 1.5, 2, and 2.5 hours, and the P values were 0.046, 0.001, and 0.005, respectively. The Cmax of QTP was significantly lower in the group comedicated with TDZ (776.9 ± 175.2 versus 1452.3 ± 707.5 ng/mL; P = 0.002). The oral clearance of QTP was significantly higher in the combined group than in the monothreapy group (123.3 ± 66.8 versus 60.3 ± 28.5 L/h; P = 0.03). Other pharmacokinetic parameters were not significantly different.
  
  
  CONCLUSIONS
  The coadministration of TDZ significantly decreased plasma QTP level and significantly increased the oral clearance of QTP. Although TDZ is switched to QTP, choosing larger doses of QTP for titration may be necessary to avoid the emergence of psychotic symptoms among schizophrenic patients.
authors.affiliation: Department of Psychiatry, Wan Fang Medical Center, Taipei, Taiwan.
authors.forename: Shen-Chieh
authors.initials: SC
authors.lastname: Chang
authors.forename: Mong-Liang
authors.initials: ML
authors.lastname: Lu
authors.forename: Yue-Chi
authors.initials: YC
authors.lastname: Wang
authors.forename: Fang-Wei
authors.initials: FW
authors.lastname: Lin
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Huang
authors.forename: Pei-Hsin
authors.initials: PH
authors.lastname: Kuo
authors.forename: Hsiu-O
authors.initials: HO
authors.lastname: Ho
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Wu
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood; D003987:Dibenzothiazepines / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000097:blood*; D004347:Drug Interactions / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D013624:Taiwan / Q000453:epidemiology; D013881:Thioridazine / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D013881:Thioridazine