Clinical trial NCT00395499: Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
Official title: Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Patients Already Taking Risperidone for Clinical Indications
Keywords: Risperidone
9-Hydroxyrisperidone
Plasma
Saliva
children
Lead sponsor: Ohio State University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2006-11-03
Enrollment: 19
Sex: ALL
Minimum age (years): 4
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief 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).

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: General Clinical Research Center
state: Ohio
city: Columbus
country: United States
facility: The Nisonger Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Michael G. Aman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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