Nefazodone pharmacokinetics in depressed children and adolescents.
OBJECTIVE
To describe the pharmacokinetics and safety of nefazodone (NFZ) in depressed children and adolescents.


METHODS
Depressed youths aged 7 to 17 years were eligible to participate. Intensive sampling for pharmacokinetic analyses of NFZ and 3 of its active metabolites was performed after single and multiple dose administration. Treatment was continued for 6 more weeks and titrated to maximize clinical response.


RESULTS
Twenty-eight patients were enrolled. Systemic exposure to NFZ and 3 metabolites was generally higher in children than adolescents. NFZ and metabolite disposition profiles showed high intra- and interpatient variability. Compared to published data in adults, the half-life of NFZ and 2 of its metabolites appears shorter in children and adolescents. Meta-chlorphenylpiperazine pharmacokinetic parameters were different in 5 patients determined to be poor metabolizers of cytochrome P450 2D6 (CYP2D6). NFZ was well tolerated, and administration was associated with significant reductions (p < .001) in depressive symptoms.


CONCLUSIONS
The pharmacokinetics of NFZ in pediatric patients is highly variable. 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 increased risk for NFZ-associated adverse events. Open-label treatment of NFZ is associated with reductions in depressive symptoms.
Findling
R L
RL
Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Preskorn
S H
SH
Marcus
R N
RN
Magnus
R D
RD
D'Amico
F
F
Marathe
P
P
Reed
M D
MD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D010879:Piperazines; D016896:Treatment Outcome; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D010879:Piperazines; D014230:Triazoles; C051752:nefazodone; D019389:Cytochrome P-450 CYP2D6