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Paroxetine pharmacokinetics in depressed children and adolescents.

OBJECTIVE
To describe the pharmacokinetics and safety of paroxetine in children and adolescents and to explore the role of genetic polymorphisms in paroxetine pharmacokinetics.


METHOD
Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and catechol-O-methyltransferase were collected. A single 10-mg dose of paroxetine was then administered followed by 5 days of blood and urine collection for pharmacokinetic analyses. Subjects subsequently received open treatment for 8 weeks, and weekly blood samples were obtained for plasma concentration measurements.


RESULTS
There was tremendous interindividual variability in paroxetine disposition. The mean half-life of paroxetine was 11.1 +/- 5.2 (SD) hours. The average clearance was 88.7 +/- 66.4 mL/min/kg. The mean area under the plasma drug concentration curve was 0.09 +/- 0.10 microgram/mL.hr. Within-subject variability of plasma paroxetine concentrations was generally not significant. Clearance and fractional urinary excretion of paroxetine were found to correlate with CYP2D6 activity. Two subjects developed hypomania necessitating drug discontinuation. No clinically significant changes in any safety assessments were noted.


CONCLUSIONS
Paroxetine is more rapidly cleared in youths than adults and may be given once daily in this population. Short-term treatment with paroxetine appears safe and well tolerated in this relatively small sample of pediatric patients.