title: QT prolongation of the antipsychotic risperidone is predominantly related to its 9-hydroxy metabolite paliperidone.
abstract: OBJECTIVE
  A dose-dependent increase in risk of sudden cardiac death for the antipsychotic drug risperidone was reported. However, few reports have so far addressed QT prolongation associated with the use of risperidone or its major active metabolite, which is also used as a separate antipsychotic drug, paliperidone.
  
  
  METHODS
  The present study evaluated associations between risperidone metabolism and QT interval in 61 psychiatric patients who had been receiving risperidone for ≥4 weeks at an average dosage of 4.7 mg/day. Plasma risperidone and paliperidone levels were measured and electrocardiographic measurements were also obtained.
  
  
  RESULTS
  There was no correlation between risperidone dosage and QTc or plasma risperidone levels and QTc. However, there was a significant positive correlation between plasma paliperidone levels and QTc (r = 0.361; p = 0.004). There was no correlation between age and dose-corrected plasma risperidone levels or between age and QTc. There was a significant positive correlation between age and dose-corrected plasma paliperidone levels (r = 0.290; p = 0.023).
  
  
  CONCLUSIONS
  Clinically, paliperidone is considered to play a more important role in QT prolongation than risperidone.
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Fukui
authors.forename: Junzo
authors.initials: J
authors.lastname: Watanabe
authors.forename: Shin
authors.initials: S
authors.lastname: Ono
authors.forename: Takuro
authors.initials: T
authors.lastname: Sugai
authors.forename: Nobuto
authors.initials: N
authors.lastname: Tsuneyama
authors.forename: Mami
authors.initials: M
authors.lastname: Saito
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects* / Q000493:pharmacokinetics; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000009:adverse effects* / Q000493:pharmacokinetics; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate