Plasma Pharmacokinetic Characteristics of Risperidone and Their Relationship to Saliva Concentrations in Children with Psychiatric or Neurodevelopmental Disorders
| Autor: | Krista Malone, Bart Remmerie, Ronald L. Lindsay, Yaser Ramadan, Erik Mannaert, Michael G. Aman, Alexander A. Vinks, Jessica Masty |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Saliva Adolescent Genotype medicine.drug_class Developmental Disabilities Atypical antipsychotic Pharmacology Article Pharmacokinetics Internal medicine Paliperidone Palmitate Blood plasma medicine Humans Pharmacology (medical) Child Psychiatry Active metabolite Risperidone business.industry Mental Disorders Dopamine antagonist Half-life Isoxazoles Pyrimidines Endocrinology Cytochrome P-450 CYP2D6 Area Under Curve Child Preschool Female business Antipsychotic Agents Half-Life medicine.drug |
| Zdroj: | Clinical Therapeutics. 29:1476-1486 |
| ISSN: | 0149-2918 |
| DOI: | 10.1016/j.clinthera.2007.07.026 |
| Popis: | Background: Risperidone is a second-generation antipsychotic agent widely used in the treatment of schizophrenia and other psychotic disorders in adults. Risperidone is probably the most frequently used atypical antipsychotic in the pediatric population. Objectives: The goals of this study were to estimate the pharmacokinetic parameters of risperidone and its enantiomers in a pediatric population and explore relationships between saliva and plasma concentrations. Methods: Eligible patients, between 4 and 15 years of age, included those taking a stable dose of oral risperidone ranging from 0.01 to 0.07 mg/kg BID for ≥4 weeks to treat psychiatric or neurodevelopmental conditions. A trough blood level and predose saliva sample were collected at study initiation; the regular risperidone dose was administered; and paired samples of blood and saliva were collected at 1, 2, 4, and 7 hours postdose. Plasma/saliva concentrations of risperidone and enantiomers of its principal active metabolite, 9-hydroxyrisperidone (9-OH-risperidone), were measured using a chiral liquid chromatography-tandem mass spectrometry assay. Standard pharmacokinetic parameters were calculated. Cytochrome P450 2D6 genotypes of *3,*4,*5 deletion and duplication were determined. Results: The study included 19 patients (age range, 4 years 2 months to 15 years 11 months). Mean (SD) values for C max , t 1/2 , and AUC 0 to 12 hours for risperidone in plasma were 15.9 (22.2) ng/mL, 3.0 (2.3) h, and 92.1 (200.6) ng · h/mL, respectively. Corresponding values in saliva were 12.0 (21.0) ng/mL, 3.4 (3.2) h, and 27.8 (38.7) ng · h/mL, respectively. Mean (SD) plasma enantiomer values for C max and AUC calculated up to the last observation were: (+)-9-OH-risperidone, 13.6 (10.0) ng/mL and 73.6 (52.3) ng · h/mL; (−)-9-OH-risperidone, 4.9 (3.1) ng/mL and 29.3 (19.1) ng · h/mL. Corresponding enantiomer values in saliva were: (+)-9-OH-risperidone, 5.2 (8.8) ng/mL and 15.6 (8.9) ng · h/mL; (−)-9-OH-risperidone, 5.0 (7.9) ng/mL and 15.6 (9.1) ng · h/mL, respectively. Large interindividual variability in risperidone and enantiomer concentrations was noted. A highly significant relationship between predose plasma and predose saliva risperidone concentrations was observed. The logarithmic regression model indicated that the log risperidone saliva concentration=−0.100 + 0.594 · log plasma concentration ( R 2 = 0.93 [Spearman]). Conclusions: In this preliminary pharmacokinetic study of parameters for risperidone and the enantiomers of 9-OH-risperidone in a pediatric population, mean C max and t 1/2 of risperidone were generally similar to those previously described in adults. The highly significant relationship between predose plasma and predose saliva risperidone concentrations suggests that saliva measurements may be a viable alternative to plasma sampling in children. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect