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- Title
PIII-56.
- Authors
Vinks, A. A.; Mannaert, E.; Pappas, K.; Aman, M. G.
- Abstract
Background: Despite widespread use of risperidone for disruptive behavior disorders in children and adolescents no pharmacokinetic (PK) data for this age group are available. The objective of the study was to determine the PK of RIS and its active metabolites (+)- and (−)- 9-hydroxy-RIS in pediatric patients.Methods: Patients participated in an open-label, Phase-1 trial. PK samples were drawn at steady-state at pre-dose, 1, 2, 4 and 7h post dose. RIS and (+)- and (−)- 9-hydroxy-RIS plasma concentrations were analyzed by LC-MS/MS. PK data analysis was performed using standard non-compartmental methods (WinNonlin Professional). CYP2D6 genotyping was performed according to published methods.Results: 19 patients, mean age 9.9y (range 4.2-15.9y) weighing 42.7 ± 17.3 Kg, were enrolled. Mean RIS Cmax concentrations were 15.9 ± 22.2 μg/L (range 2.4-104 μg/L) and pre-dose troughs 8.3 ± 20.4 μg/L (range 0.4-78.4 μg/L). Hydroxy-metabolites maximum concentrations were 13.24 ± 9.98 μg/L for (+)-9-OH-RIS (at 2h) and 4.64 ± 2.87 μg/L for (−)-9-OH-RIS (at 4h), respectively. Pre-dose concentrations were 6.6 ± 4.3 μg/L for (+)-OH-RIS and 3.81 ± 2.39 μg/L for (−)-OH-RIS, respectively. PK see Table 1.Conclusions: Mean RIS oral clearance was higher than reported in adults. Large inter-individual variability in PK profiles and dose normalized AUCs was noted. PM status resulted in 8-10 fold higher RIS concentrations and AUC. These population PK-PG data will aid in the better design of age appropriate dosing regimens.Clinical Pharmacology & Therapeutics (2005) 79, P73–P73; doi: 10.1016/j.clpt.2005.12.264
- Subjects
PHARMACEUTICAL research; PHARMACOKINETICS; PHARMACOLOGY; RISPERIDONE; ANTIPSYCHOTIC agents; THERAPEUTICS
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP73
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.264