Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
Information source: Ohio State University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Patients Already Taking Risperidone for Clinical Indications
Intervention: Risperidone (Drug)
Phase: N/A
Status: Completed
Sponsored by: Ohio State University Official(s) and/or principal investigator(s): Michael G. Aman, PhD, Principal Investigator, Affiliation: Ohio State University
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.
Clinical Details
Official title: Measurement of Risperidone and 9-Hydroxyrisperidone in Plasma and Saliva
Study design: Observational Model: Natural History, Time Perspective: Longitudinal
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
Minimum age: 4 Years.
Maximum age: 14 Years.
Gender(s): Both.
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.
Locations and Contacts
General Clinical Research Center, Columbus, Ohio 43210, United States
The Nisonger Center, Columbus, Ohio 43210, United States
Additional Information
Related publications: Aman MG, Paxton JW, Werry JS. Fluctuations in steady-state phenytoin concentrations as measured in saliva in children. Pediatr Pharmacol (New York). 1983;3(2):87-94. Aman MG, Werry JS, Paxton JW, Turbott SH, Stewart AW. Effects of carbamazepine on psychomotor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia. 1990 Jan-Feb;31(1):51-60. Aman MG, Werry JS, Paxton JW, Turbott SH. Effects of phenytoin on cognitive-motor performance in children as a function of drug concentration, seizure type, and time of medication. Epilepsia. 1994 Jan-Feb;35(1):172-80. Dumortier G, Lochu A, Zerrouk A, Van Nieuwenhuyse V, Colen de Melo P, Roche Rabreau D, Degrassat K. Whole saliva and plasma levels of clozapine and desmethylclozapine. J Clin Pharm Ther. 1998 Feb;23(1):35-40. Grant S, Fitton A. Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs. 1994 Aug;48(2):253-73. Review. Haeckel R, Hänecke P. Application of saliva for drug monitoring. An in vivo model for transmembrane transport. Eur J Clin Chem Clin Biochem. 1996 Mar;34(3):171-91. Review. Lane HY, Chang WH. Risperidone-carbamazepine interactions: is cytochrome P450 3A involved? J Clin Psychiatry. 1998 Aug;59(8):430-1. Lynn RK, Olsen GD, Leger RM, Gordon WP, Smith RG, Gerber N. The secretion of methadone and its major metabolite in the gastric juice of humans: comparison with blood and salivary concentrations. Drug Metab Dispos. 1976 Sep-Oct;4(5):504-9. Marder SR. Facilitating compliance with antipsychotic medication. J Clin Psychiatry. 1998;59 Suppl 3:21-5. Review. Nagasaki T, Ohkubo T, Sugawara K, Yasui N, Furukori H, Kaneko S. Determination of risperidone and 9-hydroxyrisperidone in human plasma by high-performance liquid chromatography: application to therapeutic drug monitoring in Japanese patients with schizophrenia. J Pharm Biomed Anal. 1999 Mar;19(3-4):595-601. Paxton JW, Aman MG, Werry JS. Fluctuations in salivary carbamazepine and carbamazepine-10,11-epoxide concentrations during the day in epileptic children. Epilepsia. 1983 Dec;24(6):716-24. Paxton JW, Donald RA. Enzyme immunoassay of carbamazepine in serum and saliva. J Pharmacol Methods. 1980 Jun;3(4):289-96. Paxton JW, Whiting B, Stephen KW. Phenytoin concentrations in mixed, parotid and submandibular saliva and serum measured by radioimmunoassay. Br J Clin Pharmacol. 1977 Apr;4(2):185-91. Walson PD, Mimaki T, Curless R, Mayersohn M, Perrier D. Once daily doses of phenobarbital in children. J Pediatr. 1980 Aug;97(2):303-5. Zuidema J, Höld KM, de Boer D, Maes RA. Saliva as a specimen for therapeutic drug monitoring in pharmacies. Pharm World Sci. 1996 Dec;18(6):193-4. Review.
Starting date: May 2001
Last updated: November 2, 2006
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