Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Ohio State University
ClinicalTrials.gov Identifier:
NCT00395499
First received: November 2, 2006
Last updated: NA
Last verified: March 2002
History: No changes posted
  Purpose

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.


Condition Intervention
Patients Already Taking Risperidone for Clinical Indications
Drug: Risperidone

Study Type: Observational
Study Design: Observational Model: Natural History
Time Perspective: Longitudinal
Official Title: Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva

Resource links provided by NLM:


Further study details as provided by Ohio State University:

Estimated Enrollment: 19
Study Start Date: May 2001
Estimated Study Completion Date: April 2003
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).

  Eligibility

Ages Eligible for Study:   4 Years to 14 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • aged 4 to 14 years, inclusive
  • male or female
  • any type of psychiatric diagnosis
  • maintained on risperidone monotherapy for at least four weeks
  • no medication adjustments for the last two weeks
  • must be taking risperidone on a twice daily (morning and evening) schedule.

Exclusion Criteria:

  • significant medical condition (e.g., heart disease, hypertension, liver or renal failure, pulmonary disease, unstable seizure disorder)
  • females of child-bearing potential who score positive of pregnancy test
  • receiving concurrent medications that may either bind to or are a substrate for CYP 450 2D6 or inhibit/induce CYP 3A3/4 activity. These include: anti-HIV medications, azole antifungal medications, calcium channel antagonists, carbamazepine, cimetidine, macrolide antibiotics (erythromycin, clarithromycin), phenytoin, propoxyphene, rifampin, or tramadol.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00395499

Locations
United States, Ohio
The Nisonger Center
Columbus, Ohio, United States, 43210
General Clinical Research Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University
Investigators
Principal Investigator: Michael G. Aman, PhD Ohio State University
  More Information

Additional Information:
Publications:

ClinicalTrials.gov Identifier: NCT00395499     History of Changes
Other Study ID Numbers: 2000H0115
Study First Received: November 2, 2006
Last Updated: November 2, 2006
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University:
Risperidone
9-Hydroxyrisperidone
Plasma
Saliva
children

Additional relevant MeSH terms:
Risperidone
9-hydroxy-risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on August 28, 2014