ABSTRACT
Title
Effect of gender and age on risperidone plasma concentrations in pediatric patients with psychotic disorders
Authors
C. D’Arrigo1, V. Santoro1, A. Gagliano2, E. Germanò2, R. Siracusano2, and E. Spina1,3
1Department of Clinical and Experimental Medicine and Pharmacology, Pharmacology Unit, University of Messina,2Division of Child Neurology and Psychiatry, University of Messina, and 3IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy
1Department of Clinical and Experimental Medicine and Pharmacology, Pharmacology Unit, University of Messina,2Division of Child Neurology and Psychiatry, University of Messina, and 3IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy
Abstract
Second-generation antipsychotics are increasingly used in child and adolescent psychiatry. Risperidone is probably the most frequently used second-generation antipsychotic in the pediatric population. Limited information is available on the steady-state plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, in children and adolescents. Aim of the present investigation was to examine the factors affecting plasma concentrations of risperidone and its metabolite in paediatric patients treated with risperidone by using data from a therapeutic drug monitoring service.
Samples from children and adolescents treated with risperidone over a period of 3 years (January 2008-December 2010) were considered for this retrospective study. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured by HPLC. Total plasma risperidone concentration was defined as the sum of plasma risperidone and 9-hydroxyrisperidone concentrations (active moiety).
The overall sample included 110 patients (77 males and 33 females, aged 5 to 18 years) which provided a total of 217 (1 to 9 measures per patient) steady-state plasma concentrations. The dose of risperidone ranged from to 0.5 to 6 mg/day (mean dose ± SD = 1.8 ± 1.1 mg/day). In the overall sample, plasma concentrations of risperidone ranged from 1 to 40 ng/ml, those of 9-hydroxyrisperidone from 1 to 72 ng/ml and those of the active moiety from 3 to 76 ng/ml. Dose-normalized total plasma risperidone concentrations were higher in females than in males (17.9 ± 11.1 vs 13.7 ± 11.5 ng/ml per mg; p<0.05).). Dose-normalized concentrations of risperidone active fraction were not correlated with age.
This study revealed a large interindividual variability in plasma concentrations of risperidone and its active metabolite in pediatric patients. Gender had a significant effect on total plasma risperidone concentrations with female patients reaching higher plasma concentrations than male patients. This gender-related pharmacokinetic effect of risperidone may be clinically relevant, as the risperidone-induced increase in prolactin levels is more pronounced in children and adolescents. On the other hand, age did not affect plasma concentrations of risperidone. Future prospective studies are necessary to clarify whether the prescribed dosage should be different in males and females.
Samples from children and adolescents treated with risperidone over a period of 3 years (January 2008-December 2010) were considered for this retrospective study. Plasma concentrations of risperidone and 9-hydroxyrisperidone were measured by HPLC. Total plasma risperidone concentration was defined as the sum of plasma risperidone and 9-hydroxyrisperidone concentrations (active moiety).
The overall sample included 110 patients (77 males and 33 females, aged 5 to 18 years) which provided a total of 217 (1 to 9 measures per patient) steady-state plasma concentrations. The dose of risperidone ranged from to 0.5 to 6 mg/day (mean dose ± SD = 1.8 ± 1.1 mg/day). In the overall sample, plasma concentrations of risperidone ranged from 1 to 40 ng/ml, those of 9-hydroxyrisperidone from 1 to 72 ng/ml and those of the active moiety from 3 to 76 ng/ml. Dose-normalized total plasma risperidone concentrations were higher in females than in males (17.9 ± 11.1 vs 13.7 ± 11.5 ng/ml per mg; p<0.05).). Dose-normalized concentrations of risperidone active fraction were not correlated with age.
This study revealed a large interindividual variability in plasma concentrations of risperidone and its active metabolite in pediatric patients. Gender had a significant effect on total plasma risperidone concentrations with female patients reaching higher plasma concentrations than male patients. This gender-related pharmacokinetic effect of risperidone may be clinically relevant, as the risperidone-induced increase in prolactin levels is more pronounced in children and adolescents. On the other hand, age did not affect plasma concentrations of risperidone. Future prospective studies are necessary to clarify whether the prescribed dosage should be different in males and females.