Predictors of risperidone and 9-hydroxyrisperidone serum concentration in children and adolescents

Chadi Albert Calarge; Del D Miller

doi:10.1089/cap.2010.0038

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Predictors of risperidone and 9-hydroxyrisperidone serum concentration in children and adolescents

Journal article

Open access

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Predictors of risperidone and 9-hydroxyrisperidone serum concentration in children and adolescents

Chadi Albert Calarge and Del D Miller

Journal of child and adolescent psychopharmacology, Vol.21(2), pp.163-169

04/2011

DOI: 10.1089/cap.2010.0038

PMCID: PMC3080754

PMID: 21486167

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Abstract

Little is known about risperidone metabolism in a clinical sample, where polypharmacy is common. Such knowledge is important since several of its side effects are dose dependent. Medically healthy patients aged 7 to 17 years old treated with risperidone for at least 6 months were enrolled. Trough serum risperidone and 9-hydroxyrisperidone concentrations were measured. One hundred seven participants (92% males) were recruited, representing a heterogenous clinical group with attention-deficit/hyperactivity disorder, disruptive behavior disorders, pervasive developmental disorders, anxiety disorders, mood disorders, tic disorders, or psychotic disorders. Risperidone had been used at a mean dose of 0.03 mg/kg, for a mean 2.5 years, predominantly to treat irritability and aggression. Cytochrome CYP2D6 inhibitors were divided into prominent (fluoxetine, bupropion, and lamotrigine), intermediate (sertraline), and weak inhibition groups (citalopram or escitalopram). The concentrations of risperidone and its metabolite were strongly associated with the dose of risperidone and time since the last dose and, to a lesser extent, with male sex. In addition, risperidone concentration increased with pubertal stage (p < 0.05), while body mass index z-score (p = 0.001) predicted a higher 9-hydroxyrisperidone concentration. The use of CYP2D6 inhibitors was much more strongly associated with risperidone concentration (p < 0.0001) than with its metabolite's (p = 0.06). In chronically treated youths, the metabolism of risperidone depends on the stage of sexual development, whereas that of 9-hydroxyrisperidone varies with body fat. Moreover, CYP2D6 inhibitors more strongly affect risperidone metabolism than that of its metabolite. The clinical implications of these findings, in relation to efficacy and tolerability, deserve further investigation.

Cytochrome P-450 CYP2D6 Inhibitors

Antipsychotic Agents - blood

Pyrimidines - blood

Antipsychotic Agents - adverse effects

Humans

Risperidone - pharmacokinetics

Male

Mental Disorders - complications

Child Development Disorders, Pervasive - drug therapy

Polypharmacy

Risperidone - therapeutic use

Antipsychotic Agents - therapeutic use

Risperidone - adverse effects

Aging

Isoxazoles - blood

Female

Risperidone - blood

Drug Therapy, Combination

Child

Body Mass Index

Isoxazoles - pharmacokinetics

Paliperidone Palmitate

Antipsychotic Agents - pharmacokinetics

Psychotic Disorders - genetics

Child Development Disorders, Pervasive - genetics

Mental Disorders - drug therapy

Pyrimidines - therapeutic use

Adolescent

Pyrimidines - adverse effects

Sex Factors

Cytochrome P-450 CYP2D6 - metabolism

Pyrimidines - pharmacokinetics

Sexual Development - physiology

Psychotic Disorders - drug therapy

Isoxazoles - therapeutic use

Isoxazoles - adverse effects

Details

Title: Subtitle: Predictors of risperidone and 9-hydroxyrisperidone serum concentration in children and adolescents
Creators: Chadi Albert Calarge - Department of Psychiatry, The University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. chadi-calarge@uiowa.edu
Del D Miller
Resource Type: Journal article
Publication Details: Journal of child and adolescent psychopharmacology, Vol.21(2), pp.163-169
DOI: 10.1089/cap.2010.0038
PMID: 21486167
PMCID: PMC3080754
NLM abbreviation: J Child Adolesc Psychopharmacol
ISSN: 1044-5463
eISSN: 1557-8992
Publisher: United States
Grant note: RR024979 / NCRR NIH HHS R21MH080968 / NIMH NIH HHS K23MH085005 / NIMH NIH HHS
Language: English
Date published: 04/2011
Academic Unit: Psychiatry
Record Identifier: 9984003922902771

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