Dose-related concentrations of neuro-/psychoactive drugs expected in blood of children and adolescents.

PURPOSE: Therapeutic drug monitoring (TDM) is highly recommended for children and adolescents treated with neuro-/psychotropic drugs. For interpretation of TDM results, drug concentrations (C/D) expected in a "normal" population are helpful to identify pharmacokinetic abnormalities or non-adherence. Using dose-related concentration (DRC) factors obtained from pharmacokinetic data, C/D ranges expected under steady state can be easily calculated by multiplication of DRC by the daily dose. DRC factors, however, are defined only for adults so far. Therefore, it was the aim of this study to estimate DRC factors for children and adolescents and compare them with those of adults.

METHODS: To obtain pharmacokinetic data (apparent total clearance of drugs from plasma after oral administration, elimination half-life, area under the curve, minimum serum drug concentration) from children and adolescents treated with psychotropic drugs, a systematic review of published literature was carried out, and the pharmaceutical companies that market these drugs were contacted. Available information was used for the calculation of DRC factors.

RESULTS: Fourteen out of 26 drugs had similar DRC factors to those reported for adults; eight and four had higher and lower factors, respectively. The antidepressants citalopram, clomipramine, fluvoxamine, and imipramine, and the antipsychotics haloperidol and olanzapine showed higher DRC factors than those calculated for adults. The DRC factors of amphetamine and methylphenidate were higher in children (6-12 years) but not in adolescents (13-17 years). On the contrary, the antipsychotic quetiapine and the mood-stabilising antiepileptics lamotrigine, oxcarbazepine, and topiramate showed lower DRC factors than those calculated for adults.

CONCLUSIONS: It was concluded that concentrations of neuro-/psychoactive drugs to be expected in blood for a given dose may differ between adults and children or adolescents, most probably owing to age-dependent differences in the elimination of these drugs.