Nefazodone pharmacokinetics in depressed children and adolescents

Objective: To describe the pharmacokinetics and safety of nefazodone (NFZ) in depressed children and adolescents. Method: Depressed youths aged 7 to 1 7 years were eligible to participate. Intensive sampling for pharmacokineti c analyses of NFZ and 3 of its active metabolites was performed after singl e and multiple dose administration. Treatment was continued for 6 more week s and titrated to maximize clinical response. Results: Twenty-eight patient s were enrolled. Systemic exposure to NFZ and 3 metabolites was generally h igher in children than adolescents. NFZ and metabolite disposition profiles showed high intra- and interpatient variability. Compared to published dat a in adults. the half-life of NFZ and 2 of its metabolites appears shorter in children and adolescents. Meta-chlorphenylpiperazine pharmacokinetic par ameters were different in 5 patients determined to be poor metabolizers of cytochrome P450 2D6 (CYP2D6). NFZ was well tolerated, and administration wa s associated with significant reductions (p < .001) in depressive symptoms. Conclusions: The pharmacokinetics of NFZ in pediatric patients is highly v ariable. NFZ appears to be safe in this small, short-term study. Pediatric patients who are poor metabolizers of CYP2D6 do not appear to be at increas ed risk for NFZ-associated adverse events. Open-label treatment of NR is as sociated with reductions in depressive symptoms.