Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents.

OBJECTIVE To determine the pharmacokinetics of fluvoxamine in children and adolescents and to compare pharmacokinetic data from adolescents to adults from a previous study. METHOD Fluvoxamine was titrated to a target dose of 100 mg b.i.d. in children (6-11 years) and 150 mg b.i.d. in adolescents (12-17 years) with obsessive-compulsive disorder or other disorder requiring fluvoxamine treatment. Serum samples were collected over 12 hours after 12 or more consecutive doses of 25, 50, 100, and 150 mg. RESULTS Sixteen children (seven females, nine males) and 18 adolescents (nine females, nine males) were included in the pharmacokinetic analyses. Children demonstrated higher mean peak plasma concentration, higher mean area under the plasma concentration-time curve, and lower apparent oral clearance compared with adolescents. Compared with male children, female children had higher mean area under the plasma concentration-time curve, higher mean peak plasma concentration, and more reports of adverse events. However, the area under the plasma concentration-time curve was not directly correlated with frequency or severity of adverse events. Pharmacokinetics were nonlinear over the dose range studied. No pharmacokinetic differences were apparent between adolescents and adults on 150 mg b.i.d. CONCLUSIONS These pharmacokinetic results suggest that children (especially females) have a higher exposure to fluvoxamine than adolescents, whereas adolescents and adults appear to have similar exposure to fluvoxamine.