Background:
Lithium is a well-established treatment for
bipolar disorders and has been shown to be neuroprotective, and thus low doses might be useful for the treatment of childhood
brain injury and neurological sequelae. However, pharmacokinetic (PK) data in children are limited. This study was to investigate the PKs after
oral administration of low-dose
lithium carbonate in young children with
intellectual disability. Methods: Fifty-two children with
intellectual disability aged 4-10 years old were enrolled. A series of blood samples were collected after a single-dose administration of
lithium carbonate. The serum
lithium concentration was measured using a validated ion chromatography assay, and the PK concentration data were modeled using a nonlinear mixed effect model in the NONMEM program. Results: The
lithium concentration over time was adequately described by a two-compartment disposition, with a transient absorption and first-order elimination process. The inclusion of
body weight as an allometric factor significantly improved the model fit, but age and gender were not associated with the PKs of
lithium. The clearance, central volume, inter-compartmental clearance, and peripheral volume estimates from the final population PK model were 0.98 L/h, 13.1 L, 0.84 L/h, and 8.2 L for children with a
body weight of 20 kg. The model evaluation suggested that there is no obvious discrepancy between the observations and predictions in the proposed model. A visual predictive check demonstrated the good predictive performance of the final model. Conclusions: The
lithium PK properties in young children were similar to those in older children and adults. The proposed model can be used for further PK/PD analysis to optimize the dosage regimen of
lithium in children.