Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
Condition: Patients Already Taking Risperidone for Clinical Indications
Study type: Observational

Summary: 
      The purpose of this research is to: (1) examine the secrection of risperidone (RIS)
      (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of
      RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in
      concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals
      during a single dosing interval.
    

Detailed description: 
      The purpose of this research is to: (1) examine the secrection of risperidone (RIS)
      (Risperdal) and its metabolite, 9-OH-RIS, in saliva, (2) determine the concentration ratio of
      RIS and 9-OH-RIS between plasma and saliva, and (3) compare the rate of decline in
      concentration of RIS and 9-OH-RIS in saliva and plasma by measurements at timed intervals
      during a single dosing interval.

      RIS is a new atypical neuroleptic agent widely used in treatment of schizophrenia and related
      disorders. It is sometimes used in serious childhood disorders as well, such as autistic
      disorder. It has a beneficial effect on both positive and negative symptoms of schizophrenia,
      accompanied by a much lower incidence of adverse effects (e.g. parkinsonism, tardive
      dyskinesia, dystonias, neuroleptic malignant syndrome). RIS is also used as a treatment of
      children with pervasive developmental disorders (PDD). RIS is metabolized to 9-OH-RIS by
      hepatic CYP2D6 which exhibits genetic polymorphism. Since RIS and 9-OH-RIS are equally
      potent, the clinical significance of CYP 2D6 status is negligible. However, in extensive
      metabolizers (EM) the T(1/2) or RIS is about 3 hrs and taht of 9-OH-RIS is approximately 20
      hrs. In poor metabolizers (PM) the half life of RIS is about 17 hrs and that of 9-OH-RIS 23
      hrs.

      Since compliance is a major problem in the management of schizophrenia, we are developing a
      rapid simplified test to measure RIS and 9-OH-RIS in salive and compare the concentration in
      samples of plasma collected concurrently. In this study, 12 adult patients (18 years and
      above) or minors (aged 5 to 17 years) already taking risperidone for clinical reasons will
      take their usual morning dose. Risperidone is usually administered once or twice a day.

      At various intervals thereafter, a 1 to 2-milliliter specimen of saliva will be removed from
      the oral cavity by means of a syringe; in some cases it is more convenient to ask volunteers
      to expel saliva into a plastic cup. We will try to cover an 18-hour interval following dosing
      for the entire group (samples will be collected at 1/4, 1/2, 1, 2, 4, 8, 12, and 18 hours
      after taking the medicine. However, only some of the samples (2 or maximum of 3) will be
      gathered from any single patient. Following collection of saliva, a sample of 2 to 4 ml of
      blood will be withdrawn, and plasma will be separated and frozen. Saliva and plasma samples
      will gathered where the patient's drug concentrations would ordinarily be collected (e.g.,
      Inpatient or Outpatient clinics, or phlebotomy laboratory). RIS concentrations will be
      measured by high pressure liquid chromatography (HPLC).
    

Intervention name(s): Risperidone
Intervention type(s): Drug
Intervention MeSH terms: Risperidone
Time perspective: Prospective
Keywords: Risperidone; 9-Hydroxyrisperidone; Plasma; Saliva; children