Paroxetine pharmacokinetics in depressed children and adolescents

Objective: To describe the pharmacokinetics and safety of paroxetine in chi ldren and adolescents and to explore the role of genetic polymorphisms in p aroxetine pharmacokinetics. Method: Thirty depressed youths were enrolled. Samples for phenotyping with respect to cytochrome P450 2D6 (CYP2D6) and ca techol-O-methyltransferase were collected. A single 10-mg dose of paroxetin e was then administered followed by 5 days of blood and urine collection fo r pharmacokinetic analyses. Subjects subsequently received open treatment f or 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 are a under the plasma drug concentration curve was 0.09 +/- 0.10 mu g/mL.hr. W ithin-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 hypoma nia necessitating drug discontinuation. No clinically significant changes i n any safety assessments were noted. Conclusions: Paroxetine is more rapidl y cleared in youths than adults and may be given once daily in this populat ion. Short-term treatment with paroxetine appears safe and well tolerated i n this relatively small sample of pediatric patients.